Individual Repertoires Research Articles

Geographic variation in songs of the Tree Pipit (Anthus trivialis) at two spatial scales

ABSTRACT. We studied geographic as well as individual variation of songs in five Czech populations of the Tree Pipit (Motacillidae: Anthus trivialis), a passerine bird with a medium-sized syllable repertoire and complex song. We focused on repertoire composition at the level of syllables (the smallest invariant song units) and of structures that are potentially important in recognition among individuals (i.e., bi-syllables, or regular repetitions of two different syllables) and among populations (introductory phrases). We tested the hypotheses that the repertoires reflect local dialects (i.e., different male origins) and that within-site similarities of male repertoires are distance dependent. The populations studied differed significantly in all analyzed characteristics. Male origin explained ∼18% of the variation in individual syllable repertoires. However, no clear within-site geographic structure in repertoire similarity was observed, either between closest neighbors or on larger scales. We observed a...

Cross-talk between transforming growth factor-β and Wingless/Int pathways in lung development and disease

Lung development depends on accurate and precise patterning of a pulmonary anlagen, consisting of both endodermally and mesodermally derived progenitor cells. In this process, the need to establish communication and control among individual cells is paramount. Transforming growth factor-β (TGFβ) and Wingless/int (Wnt) signaling pathways serve this need. The individual functional repertoire of the two pathways is further expanded by cross-talk and integration of signaling at multiple levels taking advantage of their hard-wired multi-component signal transduction platforms. Cross-talk creates the possibility for both specificity and versatility in signaling during development and during repair of injured tissue. Understanding the mechanics and the physiological implications of this cross-talk is necessary for therapeutic or preventive targeting of either TGFβ or Wnt signaling pathways.

Rural Stories about Parental Malediction (based on field materials from Novgorod and Vologda regions)

The narrative repertoire of many folk traditions features stories of children cursed by their parents. These stories can be divided into several groups with adjacent but independent plots: 1) “the substituted child:” here an unclean spirit steals a human child, replacing it with a log, a broom, or a changeling; 2) “the careless promise:” parents make a thoughtless pledge in time of crisis to give their child to the devil, who claims it when the time comes; 3) “redemption through marriage:” a child who has been cursed lives under the floorboards, in the bath house and so on until the time comes to marry. This article will concentrate on the fourth type of story, the child, who as a result of a parental curse disappears into the forest. I will be analyzing its constituent motifs and discussing the popular ideas that inspire them. The discussion is based primarily on field recordings of about seventy texts, as well as printed and archival sources. This group of stories may be defined in two different ways. According to a literal reading, these are narratives where a curse prompts the ensuing narrative, even if the maledictory formula actually appears at the end of the story, causally connecting the motifs in the tale. The second, broader interpretation encompasses all stories about children who wander or are led into the forest, even though an actual malediction may not be mentioned. These expanded subject parameters are possible because informants often tell stories about those who have been cursed in reply to questions about children lost in the forest [e.g. Belozer.-01:14. LMP],(1) or confirm that such children were described as “cursed” [Khvoin.-99:2]. I will examine the theme of children who have been cursed as a collection of related motifs, the quantity and hierarchy of which can vary from one tradition to another and be conditioned by the peculiarities of the performer’s individual narrative repertoire. Let us examine motifs of primary importance before those of secondary significance. The Inciting Incident: The Formula of the Curse

Impulsive action and motivation

This paper explores the way in which emotions are causal determinants of action. It argues that emotional events, as appraised by the individual, elicit changes in motive states (called states of action readiness), which in turn may (or may not) cause action. Actions can be elicited automatically, without prior intention (called impulsive actions), or intentionally. Impulsive actions reflect the simplest and biologically most general form in which emotions can cause action, since they require no reflection, no foresight, and no planning. Impulsive actions are determined conjointly by the nature of action readiness, the affordances perceived in the eliciting event as appraised, and the individual's action repertoire. Those actions from one's repertoire are performed that both match the perceived affordances and the aim of the state of action readiness.

An evaluation of prompt schedules and mand preference during functional communication training.

Functional Communication Training (FCT; Carr & Durand, 1985) is currently one of the most commonly utilized treatments for challenging behavior in the behavioral literature (Tiger, Hanley, & Bruzek, 2008). FCT is typically implemented following the identification of the function(s) of challenging behavior via functional assessment. Following the functional assessment, the identified functional reinforcement is made contingent on an appropriate communicative response (mand) and withheld following occurrences of challenging behavior. FCT and various mechanisms that influence the treatment's effectiveness have been evaluated within many second-generation studies following the seminal study published by Carr & Durand (1985). These include reinforcement-based components such as the role of extinction (Fisher et al., 1993; Wacker, et al., 1990) and punishment (Wacker et al., 1990); and topography-based variables such as effort associated with various mands (Buckley & Newchok, 2005; Richman, Wacker, & Winborn, 2001), the relative novelty of mands in an individual's behavioral repertoire (Winborn, Wacker, Richman, Asmus, & Geier, 2002), preference for various available mands (Winborn-Kemmerer, Ringdahl, Wacker, & Kitsukawa, 2009), and the relative proficiency with which individuals use various mand topographies (Ringdahl et al., 2009). In addition, several second-generation studies have evaluated the role of various antecedent variables on the effectiveness of FCT (e.g., Fisher, Kuhn, & Thompson, 1998; Lerman, Vorndran, Addison, & Kuhn, 2004; Peyton, Lindauer, & Richman, 2005). For example, several studies have evaluated various prompt parameters including prompt type (Lerman et al.; Peyton et al.) and schedule of prompting (Johnson, McComas, Thompson, & Symons, 2004). Specifically, Johnson et al. provided preliminary evidence of the effect of prompt schedule on mands during FCT. In that study, the experimenters implemented FCT in which both aggression and mands were reinforced on concurrent FR1 schedules of reinforcement. Initially, mand prompts were delivered on a VT 75 s schedule and mands were exhibited at low rates (i.e., 0.3 responses per minute; RPM) while aggression was exhibited at comparatively higher rates (i.e., 1.1 RPM). When prompts for manding were delivered on a FT 10s schedule, the mean rate of mands increased to 1.2 RPM while the mean rate of aggression decreased to 0.1 RPM. Although Johnson et al.'s results suggested the important role that prompt schedules likely play in mand allocation during FCT, it was not a primary focus of the study and the effects of prompt schedules were not experimentally established. Other research has focused on the effect of concurrent schedules on responding (e.g., Worsdell, Iwata, Hanley, Thompson, & Kahng, 2000), expanding the understanding of the interaction between reinforcement schedules and appropriate communicative behavior. Concurrent schedules have also been used to demonstrate that response parameters, such as preference (e.g., Winborn-Kemmerer et al., 2009) and effort (Buckley & Newchok, 2005) among mand topographies, influences responding. For example, Buckley and Nowchok used concurrent schedules to demonstrate that a separate response-related variable, effort, can impact communicative responding during FCT. Thus, concurrent schedules may also be useful in evaluating the effects of other potentially influential dimensions such as antecedent-based parameters (e.g., prompt rate). There were two main purposes of the current study. First, we wanted to evaluate the effects of various prompt schedules on mand usage for the purpose of facilitating appropriate recruitment of reinforcement. Second, we wanted to evaluate preference for available mands across prompt schedules when identical concurrent schedules of reinforcement were in place for each mand (i.e., FR1/FR1/FR1). Method Participant and Setting Sara was a 34-year-old female diagnosed with autism and mild to moderate retardation. …

Speech and language assessment: A verbal behavior analysis.

Introduction As practitioners concerned with treating speech-language disorders, one of our primary goals is to accurately and efficiently determine which communication skills should be targeted for intervention. How do we know when something needs to be taught? What defines a skill deficit or a communication breakdown ? In everyday terms, a speech-language problem is signaled when a breakdown occurs in the interaction between a speaker and a listener. That is, we say that communication is successful when the outcome of an interaction is effective (i.e., functional), but when the interaction is weak and ineffective, we suspect a deficit in the repertoire of one of the communication partners. Thus, the critical aspect that defines communicative competence lies in the success of the dyad, a dynamic process comprised of functional units of discourse between a speaker and a listener, even when these roles are assumed within a single individual (e.g., Lodhi & Greer, 1989; Palmer, 1998; Skinner, 1957). Despite the fundamentally social nature of communication, assessment tools for speech-language deficits rarely take into account this requisite speaker-listener unit, nor is it routine to test for, describe, or analyze specific breakdowns in this unit. Most speech-language assessments in widespread today evaluate response topographies (forms of responses) alone, without regard for a functional analysis of the causal variables that lead to the specific topographic features of responses. Indeed, much assessment time and energy is expended in classifying speech-language performance, not by its role within a unit of functional communication between a speaker and a listener (i.e., cause and effect), but instead only by its arbitrarily-labeled categories describing non-function based properties such as word structure (e.g., nouns, verbs, plurals), modality (expressive, receptive), relationship (e.g., antonyms/synonyms, agreement), or other inferred characteristics (e.g., ellipsis, nomination, phonological process). This focus is illustrated by ASHA's (1993) definition of language disorder as an impairment in comprehension and/or of spoken, written, and/or other symbol systems. The disorder may involve (1) the form of language (phonology, morphology, and syntax), (2) the content of language (semantics), and/or (3) the function of language in communication (pragmatics) in any combination. Although function is an element of this definition, this usage of the term refers to a linguistic feature of language (pragmatics) in contrast to Skinner's analysis of function in which environmental variables describe (and thus, define) the contingent relation that accounts for each particular instance of an utterance (i.e., language). As such, linguistic descriptions are less adequate for applied work (i.e., treatments) than is Skinner's model, which specifies the variables that evoke and strengthen verbal behavior. To be sure, a thorough topographic description of an individual's speech-language repertoire may be a necessary component to plan an appropriate therapy program, but it is insufficient to accomplish the task because a key element of the evaluation is missing. Our job during assessment is to document not merely occurrences of wrong responses to assessment items, but also the speaker-listener environment (antecedent and consequent variables) in which the topography occurs. If a functional analysis of the speaker-listener exchange is omitted from the assessment, a critical part of language learning is at risk of being excluded from an effective intervention plan (Damico, 1993; Frost & Bondy, 2006; LaRue, Weiss, & Cable, 2008; Rowland & Schweigert, 1993; Spradlin & Siegel, 1982; Sundberg, 2008). Meaning defined by environmental context. The meaning of verbal behaviors is a function of their controlling variables (Hegde, 2008; Skinner, 1957). Speakers and listeners do not make mistakes, use the wrong word, or fail to generalize in the ordinary sense. …

Spontaneous activity shaped by bifurcation memory

Most songbirds learn their songs through imitation. However, what a male sings as an adult is not necessarily a complete inventory of what he memorized at some earlier point in time: songbirds commonly memorize more material than they eventually sing as adults. Work with swamp sparrows, Melospiza georgiana, first confirmed that males rehearse many of the song models to which they are exposed during the sensory phase of song acquisition but subsequently include only a subset of those rehearsed songs in their adult repertoire. This process of overproduction and selective attrition has since been demonstrated in other species as well. More recently, the persistent memory of tutor songs rehearsed but not included in the adult repertoire has been demonstrated at the neural level. Furthermore, memories of song models heard during the sensory phase of acquisition but never detected during rehearsal in the sensorimotor phase also may persist into adulthood. Here we review behavioural and neural studies of overproduction and attrition in song learning. We discuss factors that may trigger the persistence of some models and the rejection of others in an individual's repertoire and possible functional consequences of this phenomenon. Data from human speech research indicates that humans also may unconsciously retain memories of features of languages heard early in life but never spoken.

Form and Function of Communicative Behaviours in Individuals with Angelman Syndrome

There are only a few studies that have attempted to systematically document the communicative forms and functions in the repertoires of individuals with Angelman syndrome (AS). In the present study, we sent the Inventory of Potential Communicative Acts (IPCA) (Sigafoos et al. 2000a,b) to 136 families of children with AS. The IPCA aims to provide a systematic inventory and objective description of the communication forms and functions present in the child’s repertoire. Seventy-nine surveys were returned and analyzed to determine differences in the number and types of communicative forms and functions in relation to the child’s setting, genetic subtype, presence of epilepsy, age, and level of intellectual disability. The results showed significant differences in the forms and functions of reported communicative acts for individuals with AS deletion and AS disomy, epilepsy versus no epilepsy, and for individuals with severe versus profound levels of intellectual disability. Significant differences were also evident as a function of age and living situations. These data (i) suggest that the communicative phenotype associated with AS is influenced by genetic, medical, and environmental factors and (ii) may be relevant for any attempt to enhance these persons’ communicative functioning.

Positive selection optimizes the number and function of MHCII-restricted CD4+T cell clones in the naive polyclonal repertoire

T cell receptors (TCRs) on T lymphocytes in an individual bind foreign peptides bound to major histocompatibility complex (MHC) molecules expressed in that individual (designated MHC(A)). Results from radiation bone marrow chimeras and TCR transgenic mice indicate that this complex form of antigen recognition is the result of positive selection of clones with low affinity for self peptide:MHC(A) complexes during development. Here we used a sensitive peptide:MHC tetramer enrichment method to quantify the role of positive selection in the generation of the preimmune polyclonal T cell repertoire in normal individuals. We made the surprising observation that mouse and human naive T cells capable of binding to foreign peptide:MHC(A) were present at the same frequency in hosts that expressed MHC(A) or a different MHC isoform (MHC(B)). However, most of the clones in MHC(B) hosts also recognized self peptide:MHC(A) complexes. When these "alloreactive" T cells were removed from the MHC(B) repertoire via negative selection in an MHC(A) host, the number of foreign peptide:MHC(A)-binding T cells was reduced to one fifth and many of the remaining cells did not respond to the peptide. Therefore, although positive selection on MHC(A) was not required to produce foreign peptide:MHC(A)-binding clones, it had a large effect on selecting responsive clones.

Song Repertoires in a Western European Population of YellowhammersEmberiza citrinella

Abstract. Geographic variation is one of the most intensively studied bird song topics. However, our knowledge of geographical song variations in most species studied so far is very sparse, with many areas of the species-typical geographic distributions still unexplored. One striking example is the Yellowhammer: for this species most song studies have been conducted along well defined dialect borders, but almost nothing is known about its song characteristics in other regions of its broad geographic distribution. In this study, we investigated the song structure variations and stereotypes in different areas of western Belgium and northern France. We described 66 different song types (a-elements) in 45 males recorded. Each male had a unique individual repertoire consisting of 1 to 4 of these song types. This high variability at the individual level contrasted with the high homogeneity of the specific repertoire over the whole geographic distribution of the species. The evolutionary implications of such spe...

Maladaptive mood repair responses distinguish young adults with early-onset depressive disorders and predict future depression outcomes.

Clinical depression involves persistent dysphoria, implicating impaired affect regulation or mood repair failure. However, there is comparatively little information about the mood repair repertoires of individuals with histories of clinical depression, how their repertories differ from that of never-depressed people, and whether particular types of mood repair responses differentially contribute to depression risk. Adult probands who had childhood-onset depressive disorder (n=215) and controls with no history of major mental disorder (n=122) reported which specific (cognitive, behavioral, interpersonal and somatic-sensory) responses they typically deploy when experiencing sad affect, including responses known to appropriately attenuate dysphoria ('adaptive' responses) and those known to exacerbate dysphoria in the short or long run ('maladaptive' responses). Subjects were longitudinally followed and evaluated. Remitted probands and probands in depressive episodes both reported a greater number of maladaptive responses and fewer adaptive responses to their own sadness than did controls, although probands did not have an absolute deficiency of adaptive responses. Maladaptive (but not adaptive) mood repair responses predicted future increases in depression symptoms and an increased probability of a recurrent depressive episode among probands (even after controlling for several clinical predictors of course). Post-hoc analyses revealed that maladaptive non-cognitive and maladaptive cognitive mood repair response sets each predicted depression outcomes. Individuals with past and present episodes of depressive disorder report an array of cognitive and non-cognitive responses to their own sadness that are likely to exacerbate that affect, and this pattern predicts a worse course of the disorder.

A complex, but uniform O-glycosylation of the human MUC2 mucin from colonic biopsies analyzed by nanoLC/MSn

High-sensitivity glycan profiling providing detailed structural information is very important in the search for glycan disease markers. By combining a straight-forward and fast preparation protocol of mucins with high-throughput nanoLC/MS, we have been able to study the O-glycosylation of the colon MUC2 mucin from one single biopsy (approximately 5 mg wet tissue as starting material) collected from the sigmoid colon during routine colonoscopy of 25 normal control patients. This large mucin glycoprotein was recovered from the guanidinium chloride-extracted insoluble pellet, reduced and alkylated, separated by SDS-agarose polyacrylamide composite gel electrophoresis, and transferred to a PVDF membrane. The O-linked oligosaccharides of the major MUC2 monomer band were released by reductive beta-elimination and analyzed by nanoLC/mass spectrometry and MS(n). The aim was to identify the MUC2 O-glycans of the sigmoid colon and provide a comprehensive catalog of the O-glycan repertoire. More than 100 complex O-linked oligosaccharides were identified, of which some had not been described before. Most of the oligosaccharides were based on the core 3 structure with sialic acid at the 6-position of the GalNAc and the substructure Gal beta 1-3/4-GlcNAc beta 1-3(NeuAc-6)GalNAcol was found in most glycans. The most abundant components were -Gal-(Fuc)GlcNAc-3(NeuAc-6)GalNAcol, GalNAc-(NeuAc-)Gal-4/3GlcNAc-3(NeuAc-6)GalNAcol, GalNAc-3(NeuAc-6) GalNAcol, and GlcNAc-3(NeuAc-6)GalNAcol. In contrast to the O-glycans of other mucins, the sigmoid MUC2 O-glycan repertoire and relative amounts in normal individuals were relatively constant.

Multilingualism: the case for a new research focus

We have been taught and have taught for decades, that language is not set in concrete, that it is not immutable, that it is in constant flux and that it changes over time and space. Yet, when it comes to multilingualism, the focus seems to be solely on the threats to its diversity and maintenance, rather than on its ever-changing dynamics. This article aims to offer an analytical perspective on multilingualism as an evolving process, with new language combinations within individual language repertoires and the language profiles of speech communities and polities across generations and around the world.

Variation in the use of discourse markers by Chinese teaching assistants in the US

The use of discourse markers (DMs) is common in everyday native speech. If an L2 speaker wants to sound more like a native speaker, one way is to adopt the “conventional expressions” (e.g. DMs) used by native speakers in the local community. Recently a number of studies have examined DM use by native speakers of a variety of languages; however, relatively few studies have explored the use of DMs by L2 speakers and even fewer have examined L2 speakers in the study-abroad context. This study investigates the use of English DMs by six male and female Chinese L1 graduate students in a study-abroad context. The DMs examined are yeah, oh, you know, like, well, I mean, ok, right, and actually, for a total of 1422 tokens. Combining insights from variationist sociolinguistics and SLA, this study uses quantitative methods to investigate the use of DMs in two settings, TA-led discussions and sociolinguistic interviews, and examines the variable production of L2 speakers. In addition, this study also employs qualitative analysis to examine the relationship between L2 speakers’ multifaceted social identities, language attitude, and participation in the local community with their individual repertoires and frequency of DM use.

The variable immunological self: Genetic variation and nongenetic noise in Aire-regulated transcription

The Aire transcription factor plays an important role in immunological self-tolerance by mediating the ectopic expression of peripheral self-antigens by thymic medullary epithelial cells (MECs), and the deletion of thymocytes that recognize them. In Aire-deficient humans or mice, central tolerance is incomplete and multiorgan autoimmune disease results. We examined the variability of Aire's effects on ectopic transcription among individual mice of three different inbred strains. Aire's function was, overall, quite similar in the three backgrounds, although generally stronger in C57BL/6 than in BALB/c or NOD mice, and a minority of Aire-regulated genes did show clear differences. Gene expression profiling of wild-type MECs from single mice, or from the two thymic lobes of the same mouse, revealed significantly greater variability in Aire-controlled ectopic gene expression than in Aire-independent transcripts. This "noisy" ectopic expression did not result from parental or early developmental imprinting, but from programming occurring after the formation of the thymic anlage, resulting from epigenetic effects or from the stochastic nature of Aire activity. Together, genetic and nongenetic variability in ectopic expression of peripheral antigens in the thymus make for differences in the portion of self determinants presented for tolerance induction. This variable self may be beneficial in preventing uniform holes in the T-cell repertoire in individuals of a species, but at the cost of variable susceptibility to autoimmunity.

Minding the Gap

This research project examines classroom discussion in its relationship to reading as made visible through the practice of textual annotation. In order to develop a rich description of student reading/discussion processes, we targeted multiple undergraduate seminars at a liberal arts college as they encountered the first two Acts of Shakespeare's King Lear. We collected triangulated data from these class sessions including targeted reading surveys, student reading annotations, naturalistic observation of real-time seminar discussion behavior, and student reflections. Our analysis of the students' annotations relies upon reading theorist Wolfgang Iser's conceptions of interpretive gap, consistency building, and individual repertoire. Our discussion considers the theoretical implications of this local, in-depth data for the broader analysis of student reading and discussion practices.

Repertoires of lifestyle change and self‐responsibility among participants in an intervention to prevent type 2 diabetes

This paper analyses participants' accounts on their experiences of lifestyle change during and after the intervention to prevent type 2 diabetes. This paper explores whether the individual is seen as capable of autonomously seeking for a healthier lifestyle or as dependent on external controls and support. The study is based on focus group interview data collected among intervention participants one-and-a-half years after the intervention ended. Those who had been successful in the weight reduction and those whose weight had increased after the intervention were interviewed in separate interview groups. Both weight-losers and weight-gainers agreed with the health-related objectives of the intervention. Despite this agreement, we found three distinct repertoires concerning individuals' potential to proceed in and maintain lifestyle change. The hopelessness repertoire was used mainly by the weight-gainers to describe experiences where lifestyle change was seen to be very difficult. The struggle repertoire was used frequently especially by the weight-gainers but also by the weight-losers to describe struggling against external temptations and one's weaknesses. The self-governing individual repertoire was used most often by weight-losers to describe experiences where new, healthier lifestyle had to a significant extent become a routine and the individual was seen as in charge of his/her lifestyle. The study revealed that the interviewees hold an ambivalent stance towards self-responsibility. The individual was seen as both a sovereign actor and a dependent object of interventions. Most of our interviewees called for continuous controls and even surveillance but at the same time rejected the idea of authoritarian health education. This ambivalence was most clearly present in the struggle repertoire and could be a fruitful target of clarification in health interventions. For a major part of intervention participants, lifestyle change is characterized as a constant struggle and hence interventions should plan the continuation of a support system.

Molecular Determinants of Major Histocompatibility Complex Class I Complex Stability: SHAPING ANTIGENIC FEATURES THROUGH SHORT AND LONG RANGE ELECTROSTATIC INTERACTIONS

A single amino acid exchange between the major histocompatibility complex molecules HLA-B(*)2705 and HLA-B(*)2709 (Asp-116/His) is responsible for the emergence of distinct HLA-B27-restricted T cell repertoires in individuals harboring either of these two subtypes and could correlate with their differential association with the autoimmune disease ankylosing spondylitis. By using fluorescence depolarization and pK(a) calculations, we investigated to what extent electrostatic interactions contribute to shape antigenic differences between these HLA molecules complexed with viral, self, and non-natural peptide ligands. In addition to the established main anchor of peptides binding to HLA-B27, arginine at position 2 (pArg-2), and the secondary anchors at the peptide termini, at least two further determinants contribute to stable peptide accommodation. 1) The interaction of Asp-116 with arginine at peptide position 5, as found in pLMP2 (RRRWRRLTV; viral) and pVIPR (RRKWRRWHL; self), and with lysine in pOmega, as found in gag (KRWIILGLNK; viral), additionally stabilizes the B(*)2705 complexes by approximately 5 and approximately 27 kJ/mol, respectively, in comparison with B(*)2709. 2) The protonation state of the key residues Glu-45 and Glu-63 in the B-pocket, which accommodates pArg-2, affects peptide binding strength in a peptide- and subtype-dependent manner. In B(*)2705/pLMP2, protonation of Glu-45/Glu-63 reduces the interaction energy of pArg-2 by approximately 24 kJ/mol as compared with B(*)2705/pVIPR. B(*)2705/pVIPR is stabilized by a deprotonated Glu-45/Glu-63 pair, evoked by allosteric interactions with pHis-8. The mutual electrostatic interactions of peptide and HLA molecule, including peptide- and subtype-dependent protonation of key residues, modulate complex stability and antigenic features of the respective HLA-B27 subtype.

Molecular characteristics of anti-self antibody fragments against neutrophil cytoplasmic antigens from human V gene phage display libraries.

Recently it has been demonstrated that human antibody fragments with binding activities against self antigens can be isolated from repertoires of rearranged V genes from non-immunized humans. We have applied phage display technology to study the B cell repertoire for antibody activity against neutrophil cytoplasmic antigens. These antibodies may play an important role in Wegener's granulomatosis (WG) and related forms of vasculitides. Autoantibodies in patients with WG are directed against proteinase 3. The immunodominant antigen in other forms of vasculitis is myeloperoxidase, but the B cell response can also be directed against other neutrophil enzymes, e.g. lysozyme, human neutrophil elastase, lactoferrin and cathepsin G. We show here that anti-self reactivity against neutrophil cytoplasmic antigens can be detected in the rearranged V gene repertoire of healthy individuals and that the reactivity can be directed against structural related epitopes which are present on different neutrophil cytoplasmic antigens. The scFv with binding activities were sequenced and the V gene usage, the level of somatic mutations and the immunoserological characteristics of the antibody fragments are discussed. Further evidence is presented that antibody fragments consisting only of a heavy chain variable domain can recognize neutrophil cytoplasmic antigens in a specific manner. These single-domain antibody fragments were used in experiments designed to establish the relative role of the light chain variable domains in antigen binding.

T cell receptor V beta repertoire in HIV-infection individuals: lack of evidence for selective V beta deletion.

The gradual decline of CD4+ T lymphocytes in HIV-infected individuals culminates in the lethal immunosuppression of AIDS. The mechanism of CD4+ T cell loss is currently unknown, but has recently been suggested to occur as a result of an HIV-encoded superantigen which facilitates a selective deletion of T cells expressing specific V beta genes. To verify and extend such observations, peripheral blood leucocytes (PBL) from 15 HIV+ individuals, 10 of which had very low CD4 T cell counts (< 200/mm3), were analysed for T cell receptor (TCR) V beta gene expression. In contrast to a recent study, the results presented here fail to provide evidence that selective loss of V beta-bearing T cells occurs in HIV+ individuals. Furthermore, when PBL from HIV+ individuals were stimulated with Staphylococcal enterotoxin B (SEB), T cells expressing V beta subfamilies known to engage this superantigen were expanded, indicating that such cells were not deleted and were responsive to stimulation by a bacterial superantigen. Collectively, these data suggest that CD4 loss in HIV patients does not occur in a V beta-selective, superantigen-mediated fashion.