B21 Haplotype Research Articles

Two Polymorphisms Facilitate Differences in Plasticity between Two Chicken Major Histocompatibility Complex Class I Proteins

Major histocompatibility complex class I molecules (MHC I) present peptides to cytotoxic T-cells at the surface of almost all nucleated cells. The function of MHC I molecules is to select high affinity peptides from a large intracellular pool and they are assisted in this process by co-factor molecules, notably tapasin. In contrast to mammals, MHC homozygous chickens express a single MHC I gene locus, termed BF2, which is hypothesised to have co-evolved with the highly polymorphic tapasin within stable haplotypes. The BF2 molecules of the B15 and B19 haplotypes have recently been shown to differ in their interactions with tapasin and in their peptide selection properties. This study investigated whether these observations might be explained by differences in the protein plasticity that is encoded into the MHC I structure by primary sequence polymorphisms. Furthermore, we aimed to demonstrate the utility of a complimentary modelling approach to the understanding of complex experimental data. Combining mechanistic molecular dynamics simulations and the primary sequence based technique of statistical coupling analysis, we show how two of the eight polymorphisms between BF2*15∶01 and BF2*19∶01 facilitate differences in plasticity. We show that BF2*15∶01 is intrinsically more plastic than BF2*19∶01, exploring more conformations in the absence of peptide. We identify a protein sector of contiguous residues connecting the membrane bound α3 domain and the heavy chain peptide binding site. This sector contains two of the eight polymorphic residues. One is residue 22 in the peptide binding domain and the other 220 is in the α3 domain, a putative tapasin binding site. These observations are in correspondence with the experimentally observed functional differences of these molecules and suggest a mechanism for how modulation of MHC I plasticity by tapasin catalyses peptide selection allosterically.

Differential RNA expression of TLR pathway signaling pathways in macrophages from chickens stimulated with Interferon γ in disease resistant B2 haplotypes versus susceptible B19 haplotypes. (P1216)

Abstract MHC has been associated with immunity in several species and studies have demonstrated association of MHC B haplotype in chickens and resistance to a variety of viral pathogens including Marek’s disease virus, avian leucosis virus, Newcastle disease virus and Rous sarcoma virus. Previous studies in our laboratory have shown that chicks with the homozygous B2 MHC haplotypes are more resistant to respiratory illness following avian coronavirus infection, than homozygous B19 chicks. Further studies demonstrated more vigorous responses of B2 macrophages to Poly I:C and IFNγ stimulation than responses of B19 derived macrophages. Macrophages play a critical role in the early innate response and mobilization of the adaptive immune responses. Next Generation Sequencing of IFNγ stimulated macrophages show differential expression of genes of the toll-like receptor signaling pathway. Macrophages were stimulated for 0, 1, 2, 4, 8, 16, 24 and 48 hours. At most time points more genes were stimulated in macrophages of the disease resistant B2 haplotype and quantification of RNA expression (fold-increase) indicates earlier and more robust stimulation of several genes.

Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the chicken MHC class I molecule BF2*1501.

The chicken major histocompatibility complex (MHC) class I molecules named BF are strongly associated with Marek's disease (MD). A single structure, that of chicken BF2*2101 from the B21 haplotype, which might provide resistance to MD, has been determined. However, little is known about other structures apart from BF2*2101. In order to provide further structures of chicken MHC class I molecules, BF2*1501 and chicken β(2)-microglobulin complexed with a nonapeptide (MDV-MEQ(RRR9)) derived from Marek's disease virus MEQ protein (MDV EcoRI Q fragment, residues 72-80) were assembled and crystallized. Diffraction data from the crystal were collected to 2.6 Å resolution; the crystal belonged to space group P3(1)21, with unit-cell parameters a = 125.1, b = 125.1, c = 80.9 Å and two molecules in the asymmetric unit. The Matthews coefficient V(M) was 2.08 Å(3) Da(-1), with a calculated solvent content of 40.78%. These data will be helpful in obtaining insight into the structural basis of the involvement of BF2*1501 in MD.

Association of the chicken MHC B haplotypes with resistance to avian coronavirus

Clinical respiratory illness was compared in five homozygous chicken lines, originating from homozygous B2, B8, B12 and B19, and heterozygous B2/B12 birds after infection with either of two strains of the infectious bronchitis virus (IBV). All chickens used in these studies originated from White Leghorn and Ancona linages. IBV Gray strain infection of MHC homozygous B12 and B19 haplotype chicks resulted in severe respiratory disease compared to chicks with B2/B2 and B5/B5 haplotypes. Demonstrating a dominant B2 phenotype, B2/B12 birds were also more resistant to IBV. Respiratory clinical illness in B8/B8 chicks was severe early after infection, while illness resolved similar to the B5 and B2 homozygous birds. Following M41 strain infection, birds with B2/B2 and B8/B8 haplotypes were again more resistant to clinical illness than B19/B19 birds. Real time RT-PCR indicated that infection was cleared more efficiently in trachea, lungs and kidneys of B2/B2 and B8/B8 birds compared with B19/B19 birds. Furthermore, M41 infected B2/B2 and B8/B8 chicks performed better in terms of body weight gain than B19/B19 chicks. These studies suggest that genetics of B defined haplotypes might be exploited to produce chicks resistant to respiratory pathogens or with more effective immune responses.

Narrow Groove and Restricted Anchors of MHC Class I Molecule BF2*0401 Plus Peptide Transporter Restriction Can Explain Disease Susceptibility of B4 Chickens

The MHC has genetic associations with many diseases, often due to differences in presentation of antigenic peptides by polymorphic MHC molecules to T lymphocytes of the immune system. In chickens, only a single classical class I molecule in each MHC haplotype is expressed well due to coevolution with the polymorphic TAPs which means that resistance and susceptibility to infectious pathogens are particularly easy to observe. Previously, structures of chicken MHC class I molecule BF2*2101 from B21 haplotype showed an unusually large peptide-binding groove that accommodates a broad spectrum of peptides to present as epitopes to CTLs, explaining the MHC-determined resistance of B21 chickens to Marek's disease. In this study, we report the crystal structure of BF2*0401 from the B4 (also known as B13) haplotype, showing a highly positively charged surface hitherto unobserved in other MHC molecules, as well as a remarkably narrow groove due to the allele-specific residues with bulky side chains. Together, these properties limit the number of epitope peptides that can bind this class I molecule. However, peptide-binding assays show that in vitro, BF2*0401 can bind a wider variety of peptides than are found on the surface of B4 cells. Thus, a combination of the specificities of the polymorphic TAP and the MHC results in a very limited set of BF2*0401 peptides with negatively charged anchors to be presented to T lymphocytes.

Prediction and Identification of T Cell Epitopes in the H5N1 Influenza Virus Nucleoprotein in Chicken

T cell epitopes can be used for the accurate monitoring of avian influenza virus (AIV) immune responses and the rational design of vaccines. No T cell epitopes have been previously identified in the H5N1 AIV virus nucleoprotein (NP) in chickens. For the first time, this study used homology modelling techniques to construct three-dimensional structures of the peptide-binding domains of chicken MHC class Ι molecules for four commonly encountered unique haplotypes, i.e., B4, B12, B15, and B19. H5N1 AIV NP was computationally parsed into octapeptides or nonapeptides according to the peptide-binding motifs of MHC class I molecules of the B4, B12, B15 and B19 haplotypes. Seventy-five peptide sequences were modelled and their MHC class I molecule-binding abilities were analysed by molecular docking. Twenty-five peptides (Ten for B4, six for B12, two for B15, and seven for B19) were predicted to be potential T cell epitopes in chicken. Nine of these peptides and one unrelated peptide were manually synthesized and their T cell responses were tested in vitro. Spleen lymphocytes were collected from SPF chickens that had been immunised with a NP-expression plasmid, pCAGGS-NP, and they were stimulated using the synthesized peptides. The secretion of chicken IFN-γ and the proliferation of CD8+ T cells were tested using an ELISA kit and flow cytometry, respectively. The significant secretion of chicken IFN-γ and proliferation of CD8+ T lymphocytes increased by 13.7% and 11.9% were monitored in cells stimulated with peptides NP89–97 and NP198–206, respectively. The results indicate that peptides NP89–97 (PKKTGGPIY) and NP198–206 (KRGINDRNF) are NP T cell epitopes in chicken of certain haplotypes. The method used in this investigation is applicable to predicting T cell epitopes for other antigens in chicken, while this study also extends our understanding of the mechanisms of the immune response to AIV in chicken.

A century of poultry genetics

The 20th Century saw an astonishing advance in our understanding of genetics and the scientific basis of the genetic improvement of farm animals. The application of genetic principles to chickens in the 1950s and 1960s led to a rapid change in the productivity and efficiency of laying hens and broiler chickens, turkeys and ducks. Subsequently, the application of increasingly powerful computers and sophisticated mathematical algorithms has increased the range of traits that could be successfully incorporated into breeding programs. Random sample tests of the performance of laying hens enjoyed a period of popularity and more recently the few remaining tests included husbandry systems in addition to strain evaluation. Characterisation of avian blood groups has led to the identification of the B21 haplotype that confers resistance to Marek's disease and to selection for this locus in commercial lines. The decade following the millennium saw the publication of the genome sequence of the chicken and the identification of millions of single nucleotide polymorphisms that, coupled with technological advances, made the application of whole genome selection practical in poultry. In parallel, the molecular basis for some Mendelian traits described a century ago is now being deciphered. Similar technologies have been applied to study genetic diversity in chickens and have provided insights into the evolution and domestication of chicken breeds. Finally, in this review, the recent development of the European Poultry Genetics Symposia coordinated by Working Group 3 ‘Genetics and Breeding’ that was based on combining the British Poultry Breeders Round Table and AVIAGEN from West and Eastern Europe, is discussed.

Specific TaqMan probed real-time quantitative RT-PCR methods and their application to differentiate the transcripts of duplicated BF or BLB genes in chicken MHC

BF and BLB genes of chicken major histocompatibility complex (MHC) are responsible for classical antigen processing and presentation; therefore they play a central role in determining the genetic resistance or susceptibility of different MHC-B haplotypes to some infectious diseases. In this study, we developed specific TaqMan probed real-time quantitative reverse transcription PCR (TaqMan qRT-PCR) methods based on the diagnostic nucleotide polymorphisms present in duplicated BF or BLB genes in B2 and B19 haplotypes. The results showed very similar amplification efficiency but no cross-reaction between the duplicated BF or BLB genes of the same haplotype. Spleen mRNA samples of B2 and B19 chickens were used to validate these TaqMan qRT-PCR methods. We observed that BF2 or BLB2 gene was dominantly transcribed in all B2 and B19 chickens. Our findings verified the impact of diversified promoter sequences on the function of duplicated BF or BLB genes. Hence the principles adopted to establish these specific TaqMan qRT-PCR methods in this study can be applied to differentiate the transcripts of duplicated BF or BLB genes of other MHC-B haplotypes in chicken.

Marek's disease resistant/susceptible MHC haplotypes in Xiayan chickens identified on the basis of BLB2 PCR-RFLP and BLB2/BF2 sequence analyses

1. The aim was to analyse the variability of the BLB2/BF2 genes of Xiayan chickens to identify homozygous birds with resistance or susceptibility to Marek's disease (MD). 2. The experiment used two lines: birds from a common line were divided into Group A (unvaccinated) and Group B (vaccinated with herpesvirus of turkeys (HVT)); and birds from an MD-resistant line were divided into Group C (unvaccinated) and Group D (vaccinated with HVT). They were challenged intra-abdominally with Marek's disease virus (MDV) and genomic DNA extracted from peripheral blood lymphocytes so that polymorphism of the BLB2/BF2 genes could be analysed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) and nucleotide sequence analysis. 3. A 374-bp fragment of the BLB2 gene was amplified from the samples and, after digesting with restriction enzymes Alu I, Cai I, Cfr I, Hin1 I, Hinf I and Rsa I for RFLP analysis, the 6 electrophoretic patterns were analysed. Seven homozygous genotypes were found and used tentatively to identify alleles of the BLB2 gene. 4. A 765-bp fragment of the BF2 gene was amplified from the 7 samples for cloning and sequencing. 5. Six homozygous birds were confirmed from the sequenced BLB2/BF2 gene. Four birds were resistant to MD. Three birds had identical nucleotide sequences and were highly homologous with MHC haplotype B6, which is MD resistant. One bird had high homology with the highly MD-resistant B21 haplotype, and two birds were susceptible and highly homologous to the B19 haplotype, which is highly MD susceptible.

A great diversity of Amerindian mitochondrial DNA ancestry is present in the Mexican mestizo population

There are limited data on mitochondrial DNA (mtDNA) variation in the Mexican mestizo population. To examine the genetic diversity and matrilineal ancestry, the full mtDNA hypervariable regions I and II were sequenced in 270 unrelated mestizos from different regions of Mexico. A total of 202 different haplotypes were identified and the haplotype diversity was 0.9945. Amerindian haplotypes predominated in the sample with a proportion of 93.3%, followed by European (6.0%) and African haplotypes (0.7%). The frequency of the Amerindian haplogroups A2, B2, C1 and D1 was 51.1, 17.8, 18.5 and 5.9%, respectively. The frequency of Amerindian haplogroups was higher in the central region than in Mexico City, whereas it was the contrary for European haplogroups. This difference was accounted principally by the high frequency of B2 haplotypes in the central region. The minimum spanning network, the mismatch distribution and Tajima's D neutrality test suggest a population expansion for each Amerindian haplogroup, which could be initiated more recently for haplogroups A2 and D1. The present knowledge combined with other nuclear genetic markers will be essential in future association studies to correct for genetic substructure in mestizo populations.

MHC haplotype involvement in avian resistance to an ectoparasite

Research on immune function in evolutionary ecology has frequently focused on avian ectoparasites (e.g., mites and lice). However, host immunogenetics involved with bird resistance to ectoparasites has not been determined. The critical role of the major histocompatibility complex (MHC) in adaptive immunity and high genetic variation found within the MHC make this gene complex useful for exploring the immunogenetic basis for bird resistance to ectoparasites. The objective of this study was to determine if the avian MHC influenced resistance to a blood-feeding ectoparasite. Four congenic lines of chickens, differing only at the MHC, were comparatively infested with a cosmopolitan ectoparasite of birds-northern fowl mite (NFM)-which is also a serious pest species of poultry. Mite infestations were monitored over time and mite densities (weekly and maximum) were compared among lines. Chickens with the MHC haplotype B21 were relatively resistant to NFM, compared with birds in the B15 congenic line (P < 0.02). To test for similar effects in an outbred genetic background, a separate experiment was performed with 107 commercial chickens (white leghorn, W-36 strain) infested with NFM. Hens were genotyped using a MHC microsatellite marker (LEI0258) and associations between MHC haplotype and NFM density were tested. The highest peak NFM populations occurred more often on hens with the B15 haplotype versus the B21 haplotype (P = 0.012), which supported the results of the congenic study. These data indicate the avian MHC influences ectoparasite resistance, which is relevant to disease ecology and avian-ectoparasite interaction.

Transcriptional analysis of host responses to Marek’s disease virus infection in genetically resistant and susceptible chickens

Marek's disease virus (MDV) is a cell-associated oncogenic herpesvirus that targets B cells and T cells, inducing lymphoid tumours in chickens. Genetic resistance to Marek's disease (MD) is regulated in a polygenic fashion. In this study, we sought to compare the gene expression profiles following infection of birds that are genetically resistant or susceptible to MD (with the B21 and B19 haplotypes respectively at the MHC locus), including comparisons to uninfected controls. On days 4, 7, 14 and 21 post-infection, gene expression profiles in spleen tissue were obtained using a chicken immune-specific microarray. A number of genes showed significant (P <or= 0.05) differential expression across time and treatments. These included the chemokine AH221, B-cell marker Bu-1, IgG, IgA, IgM, MHC class II beta chain, granzyme A (GZMA) and signal transducers and activators of transcription 2 (STAT2) genes. In several comparisons, genes such as GZMA and STAT2 were induced in infected birds regardless of their genetic background. However, only immunoglobulin genes were differentially expressed by >or=2-fold in resistant compared with susceptible infected chickens. IgM and IgG were significantly induced on day 7 post-infection in susceptible chickens compared to resistant birds, whereas both of these genes were repressed in susceptible birds on day 14 post-infection. Overall, gene expression profiles in the chicken spleen observed after MDV infection were dependent on time and host genetic background. These gene expression profiles provide a platform for defining novel candidate genes for resistance or susceptibility to MD.

Salmonella as an Inducer of Autoimmunity.

A clear etiological link has been established between infection with several gram-negative enteric pathogens, including Salmonella spp., and the incidence of reactive arthritis (ReA), an autoimmune disease that largely affects the joints. ReA is sometimes referred to as Reiter's syndrome, particularly when accompanied by uveitis and urethritis. This review reviews the evidence etiologically linking Salmonella infection with autoimmune disease and addresses the roles that bacterial and host elements play in controlling disease outcome. ReA is an autoimmune disease that largely consists of painful joint inflammation but also can include inflammation of the eye, gastrointestinal tract, and skin. ReA is a member of a broad spectrum of chronic inflammatory disorders termed the seronegative spondyloarthropathies (SNSpAs) that includes ankylosing spondylitis (AS), psoriatic arthritis, and enteropathic arthritis. Salmonella species, as well as other enteric pathogens associated with postgastroenteritis ReA, are facultative intracellular gram-negative bacteria. Many studies have analyzed the association of the HLA class I molecule, HLA-B27, with SNSpAs. Whereas B27 has been shown to be present in 90 to 95% of cases of AS, the association of the B27 haplotype with other SNSpAs is more tenuous. The clear association between ReA and infection with Salmonella or other gram-negative enteric pathogens has led to the suggestion that the adaptive immune response to infection has an autoimmune component. In addition to various Salmonella species, other gram-negative enteric pathogens have been linked to the development of ReA. Given their close relationship to Salmonella, this review considers the involvement of Shigella species in ReA.

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Marek's disease.

Different Evolutionary Histories of the Two Classical Class I Genes BF1 and BF2 Illustrate Drift and Selection within the Stable MHC Haplotypes of Chickens

Compared with the MHC of typical mammals, the chicken MHC (BF/BL region) of the B12 haplotype is smaller, simpler, and rearranged, with two classical class I genes of which only one is highly expressed. In this study, we describe the development of long-distance PCR to amplify some or all of each class I gene separately, allowing us to make the following points. First, six other haplotypes have the same genomic organization as B12, with a poorly expressed (minor) BF1 gene between DMB2 and TAP2 and a well-expressed (major) BF2 gene between TAP2 and C4. Second, the expression of the BF1 gene is crippled in three different ways in these haplotypes: enhancer A deletion (B12, B19), enhancer A divergence and transcription start site deletion (B2, B4, B21), and insertion/rearrangement leading to pseudogenes (B14, B15). Third, the three kinds of alterations in the BF1 gene correspond to dendrograms of the BF1 and poorly expressed class II B (BLB1) genes reflecting mostly neutral changes, while the dendrograms of the BF2 and well-expressed class II (BLB2) genes each have completely different topologies reflecting selection. The common pattern for the poorly expressed genes reflects the fact the BF/BL region undergoes little recombination and allows us to propose a pattern of descent for these chicken MHC haplotypes from a common ancestor. Taken together, these data explain how stable MHC haplotypes predominantly express a single class I molecule, which in turn leads to striking associations of the chicken MHC with resistance to infectious pathogens and response to vaccines.

Genetic Diversity Between Red Jungle Fowl and Domestic Chicken For BL B2 Region

Singh, A., Gupta, J., Churchil, R.R., Sharma, D. and Singh, R.V. 2007. Genetic diversity between red jungle fowl and domestic chicken for BL B2 region. J. Appl. Anim. Res., 31: 69–72. Genetic polymorphism in BL B2 gene between Red Jungle Fowl (RJF) and domesticated chicken through sequence homology comparisons was studied. A 277 bp amplicon representing second exon corresponding to β extra cellular domain of BL B2 gene was amplified using chicken specific primers and sequenced (Accession No DQ885564). Sequence homology comparisons of the 277 bp sequence of RJF showed that it had the maximum genetic similarity (93.3%) with BW1 haplotype of RJF. Among the chicken B haplotypes, B21 haplotype, irrespective of its genetic background i.e. either it is from White Leghorn or Thai native chicken, showed maximum sequence homology. Among chicken breeds, RJF showed more genetic similarity with Chinese and Korean native in comparison to Indian native chicken breed.

Chicken major histocompatibility complex class II molecules of the B19 haplotype present self and foreign peptides

The chicken major histocompatibility complex (MHC), or B-complex, mediates genetic resistance and susceptibility to infectious disease. For example, the B19 haplotype is associated with susceptibility to Marek's disease. Here, we describe the sequencing and analysis of peptides presented by B19 MHC class II molecules. A B19/B19 B-cell line was used for the immunoaffinity purification of MHC class II molecules, which was followed by acid elution of the bound peptides. The eluted peptides were then analysed using tandem mass spectrometry. Thirty peptide sequences were obtained, ranging from 11 to 25 amino acids in length. Source protein cellular localization included the plasma membrane, cytosol and endosomal pathway. In addition, five peptides from the envelope glycoprotein of chicken syncytial virus (CSV) were identified. Chicken syncytial virus had been used as a helper virus along with reticuloendotheliosis virus strain T for transformation of B19/B19B cells. Alignment and analysis of the peptide sequence pool provided a putative peptide-binding motif for the B19 MHC class II.

Recurrent Glomerular Diseases After Renal Transplantation

Introduction Recurrent glomerular diseases are important causes of graft dysfunction after renal transplantation. As the outcomes of transplantation continue to improve, the problem of recurrent diseases in the transplanted kidney have become evident. The purpose of our study was to determine the risk factors for and the incidence of recurrence in the posttransplant period as well as their impact on graft survival rates. Method We retrospectively analyzed 49 patients with glomerular diseases due to membranoproliferative glomerulonephritis ( n = 26); focal segmental glomerulosclerosis (FSGS, n = 18); and systemic lupus erythematosus ( n = 5). The mean follow-up was 9.5 years. Results Recurrent disease was detected in 30 of 49 patients after a mean posttransplant follow-up of 28.1 months (range = 1 to 157) and their average graft survival was 41.3 months. Nineteen patients were recurrence-free with a mean graft survival of 79.4 (range = 15 to 158) months ( P < .05). One patient with FSGS, showed disease-recurrence in her third transplant after having experienced recurrences in the former grafts. In all six patients with HLA haplotype B8, recurrence was observed at a mean of 19.5 ± 9.8 months. The only risk factor that was identified was this HLA haplotype. Conclusion Recurrent disease a significant problem after renal transplantation is associated with decreased graft survival. The donor HLA type may be associated with risk, which should be clearly discussed with both the living donor and the recipient candidate.

Peptide motifs of the single dominantly expressed class I molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens

Compared with the MHC of typical mammals, the chicken MHC is smaller and simpler, with only two class I genes found in the B12 haplotype. We make five points to show that there is a single-dominantly expressed class I molecule that can have a strong effect on MHC function. First, we find only one cDNA for two MHC haplotypes (B14 and B15) and cDNAs corresponding to two genes for the other six (B2, B4, B6, B12, B19, and B21). Second, we find, for the B4, B12, and B15 haplotypes, that one cDNA is at least 10-fold more abundant than the other. Third, we use 2D gel electrophoresis of class I molecules from pulse-labeled cells to show that there is only one heavy chain spot for the B4 and B15 haplotypes, and one major spot for the B12 haplotype. Fourth, we determine the peptide motifs for B4, B12, and B15 cells in detail, including pool sequences and individual peptides, and show that the motifs are consistent with the peptides binding to models of the class I molecule encoded by the abundant cDNA. Finally, having shown for three haplotypes that there is a single dominantly expressed class I molecule at the level of RNA, protein, and antigenic peptide, we show that the motifs can explain the striking MHC-determined resistance and susceptibility to Rous sarcoma virus. These results are consistent with the concept of a "minimal essential MHC" for chickens, in strong contrast to typical mammals.

FAILURE TO RESPOND TO HEPATITIS B VACCINE IN CHILDREN WITH CELIAC DISEASE

Objectives: Celiac disease (CD) has strong association with specific human leukocyte antigen (HLA) haplotypes B8, DR3, DQ2 and DQ8. These haplotypes are often found in people who do not respond to hepatitis B virus (HBV) vaccine. The aim of this study is to determine whether children with CD fail to respond to HBV vaccine more frequently than children without CD. Study Design: This was a prospective study which compared the response to HBV, tetanus, rubella and Haemophilius Influenza type b (Hib) vaccines between children with CD and age/sex-matched controls. Results: There were 26 CD subjects and 18 age/sex-matched controls in the study. There was a significantly higher proportion of subjects in the CD group (14/26) with failed response to HBV vaccine than control (2/18) (53.9% vs. 11.1%; p < 0.005). Subjects with CD were 9.33 times more likely to test negative for the HBsAb than control (95% CI: 1.8,49.1). All subjects in both groups were positive for the rubella antibodies. There was only one subject in the CD group who was negative for tetanus antibody and none in the control group (3.9% vs. 0%; p = 1.0). There were fewer subjects in the CD group with negative response to Hib than the control group (33.3% vs. 44.4%; p = 0.53). Conclusion: Children with CD respond less frequently to HBV vaccines compared to age/sex-matched control.