A2 Antigen Research Articles

Mutant HLA-A2 antigens as restricting elements for virus-specific cytotoxic T cells.

Mutants of the EB virus-transformed cell line T5-1 (HLA-A1, 2; B8, 27), bearing well-characterized alterations in HLA-A2 antigen expression and unable to bind the HLA-A2-specific monoclonal antibody BB7.2, have been tested for their susceptibility to EB virus-specific cytolysis using effector T-cell preparations functionally restricted through relevant HLA antigens. Initial experiments first confirmed that the parent line T5-1 was susceptible to cytolysis by both "common" A2-restricted and B27-restricted effector cells. While those T5-1 mutants with little or no surface A2 expression were not lysed by A2-restricted effectors, those targets with quantitatively normal expression of mutant A2 molecules were as susceptible to A2-restricted lysis as the parent line itself. In contrast, all the T5-1 mutant lines were susceptible to B27-restricted cytolysis. The results demonstrate that experimentally induced mutations of HLA-A2 antigen structure, affecting a serologically defined site on the molecule, can occur without altering that same molecule's expression of the T cell-restricting determinant(s). Such experimentally induced mutations are quite different from the naturally occurring "variant" A2 antigens which are present within the serologically defined A2 antigen group and which show changes at the T cell-restricting site.

Human leukocyte antigen in genodermatosis.

Tissue typing performed on the lymphocytes of 41 patients, including: 23 patients with ichthyosis (15 of autosomal dominant and 8 of the x-linked variety; 8 patients with tuberous sclerosis (epiloia); and 10 patients with acrodermatitis enteropathica (AEP). In addition, tissue typing was performed for a control group of 80 healthy unrelated subjects of the same ethnic origin as the patients. A significant increase of A2 antigen or its crossreacting antigen A28 was detected among the three diseases studied. A significant increase of HLA-A2 antigen was found in autosomal dominant ichthyosis, while the x-linked variety showed significant association with HLA-Cw2. A significant association with HLA-A28 antigen was noticed in both epiloia and AEP. The suggested mechanisms of such association may be referred to as incidental genetic linkage with mutants causing disease or deficiency.

Epstein-Barr virus-specific cytotoxic T lymphocytes as probes of HLA polymorphism. Heterogeneity of T cell-restricting determinants associated with the serologically defined HLA-A2 antigen.

Epstein-Barr (EB) virus-specific effector T cell lines were established from nine virus-immune donors positive for the serologically defined HLA-A2 antigen; of these, four lines contained a demonstrable A2-restricted cytotoxic component. When these four effector populations were each tested on the same panel of EB virus-transformed lines from 20 HLA-A2-positive individuals, 16 of the target cell lines were consistently killed at levels above 25% of the relevant autologous cell lysis. Cytotoxicity appeared to be mediated through a restricting determinant associated with the 'common A2' antigen that these lines shared; indeed the lysis could be specifically blocked by high concentrations of an HLA-A2-specific monoclonal antibody. In contrast, 4 out of 20 target cell lines were not killed by HLA-A2-restricted effector cells, even though they did express the serologically defined A2 antigen and were found in other tests to be susceptible to EB virus-specific cytolysis restricted through other HLA-A or -B antigens on their surface. These results suggest that EB virus-specific cytotoxic T cells can distinguish between serologically identical HLA-A2 molecules via the heterogeneity of their T cell-restricting determinants. Data from one of the effector cell populations further suggested that a serologically defined cross-reaction between the otherwise distinct HLA-A2 and -Bw57 antigens might also be reflected in a cross-reactivity of T cell-restricting determinants.

Genetic control of soluble HLA antigen levels in serum.

HLA-A2, -A9, and -A10 antigen titers in serum were assessed by the lymphocytotoxicity inhibition test on family bloods of neonates (cord bloods) and parents in order to investigate their genetic control. (1) Serum HLA-A9 and -A10 antigens were distributed among parents with higher titers than neonates, while serum HLA-A2 antigen was found with almost equal titers among parents and neonates. (2) Correlation of serum HLA antigen titers was calculated between parents and neonates: A2 and A9 antigen titers showed positive correlations. AIM antigen was hardly detectable in sera of neonates. (3) Neonates whose parents were weak inhibitors had low titers of that antigen, while neonates of strong inhibitor parents had high or low titers. (4) Discrepancy was observed among the HLA antigen titers of different specificities in heterozygous individuals. It was difficult to group individuals into secretors and nonsecretors of whole HLA antigens.

Frequency of HLA antigens in Greek patients with open-angle glaucoma

50 Greek patients with primary open-angle glaucoma were tissue-typed for a total of 29 HLA antigens (groups A and B). The results were compared with those of 200 control persons. A statistically significant difference at the level of p less than 0.05 was noted only with regard to the A2 antigen. These findings are in accordance with those of other authors who found no correlation between glaucoma simplex and the frequency of HLA antigens.

Serum antibody response of ewes and their lambs to Pasteurella haemolytica.

Vaccination of pregnant ewes with a Pasteurella haemolytica adjuvanted vaccine which contained serotypes A1, A2 and A6 antigens caused significant increases in serum antibody titres to A1 and A6 measured by the indirect haemagglutination test (IHA). The response to vaccination with the serotype A2 antigen contained in this vaccine cannot be measured by the IHA test. There were also increased antibody titres in the colostrum from the vaccinated ewes and in the serum of their lambs after sucking compared with the corresponding titres in unvaccinated ewes and their lambs. The inoculation of either 10 +/- 2- or 18 +/- 2-day-old lambs from both vaccinated or unvaccinated ewes with the same vaccine induced the active production of antibodies to serotypes A1 and A6 despite the presence of passively acquired antibodies. By four weeks after vaccination the group geometric mean serum antibody titres of lambs from both vaccinated and unvaccinated were similar whether the lambs were vaccinated at 10 or 18 days of age. Successful vaccination of young lambs with this type of vaccine is therefore possible. Optimum protection would be obtained by vaccinating ewes in late pregnancy and their lambs within the first two weeks of life.

Virus-immune cytotoxic T cells recognize structural differences between serologically indistinguishable HLA-A2 molecules

The self-specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to identify the relationship between the self-determinants which they recognize and the serologically defined HLA-A and -B antigenic determinants. Virus-immune T cells were generated in vitro by culture of normal adult peripheral blood lymphocytes with A/HK influenza virus. Virus-immune effectors from HLA-A2 positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for the HLA-A2 specificity. Virus-immune T cells from 11/11 A2-positive donors lysed all 2A-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cell populations consistently failed to lyse the virus-infected target cells from ove A2-positive donor (designated M7). Although the A2 antigen of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serological analyses. Results of iscelectric focusing of A2 molecules from three individuals plus M7 demonstrated that the M7 A2 heavy polypeptide chain is structurally distinct. These results indicate that: 1) there is a strong but incomplete associatione between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity; and 2) there may be at least two structurally and functionally distinct epitopes on the same A2 molecule: one is the serologically defined HLA-A2 antigenic determinant; the other is the self determinant recognized by T cells on HLA-A2 molecules.

The self determinants recognized by human virus-immune T cells can be distinguished from the serologically defined HLA antigens.

The self specificity of human influenza virus-immune cytotoxic T cells has been analyzed in order to clarify the relationship between the self antigens that they recognize and the serologically defined HLA-A and -B antigens. Virus-immune effectors from HLA-A2-positive donors were tested on panels of virus-infected target cells from donors who were either HLA-mismatched or matched only for HLA-A2. Virus-immune T cells from 11 out of 11 A2-positive donors lysed all A2-matched virus-infected target cells (and no HLA-mismatched targets), except that each of these effector cells consistently failed to lyse virus-infected target cells from one A2-positive donor (designated M7). Although the A2 specificity of donor M7 could also be distinguished from the A2 antigen of other donors by alloimmune cytotoxic T cells, no differences in the A2 antigen of donor M7 could be defined by extensive serologic analyses. These results indicate that there is a strong but incomplete association between a self antigen recognized by virus-immune T cells and the serologically defined HLA-A2 specificity.

Linkage between HLA antigens and obesity.

We performed HLA typing in 122 obese children, 47 with a history of familial obesity and 75 with a negative history. The control group consisted of 905 subjects, without family relation with patients, living in the same geographical area. Our results show: 1)in the 47 patients with familial obesity a significant increase in HLA B13 antigen as compared to controls (p <.05), with a relative risk of 3.45; 2)in the 75 patients without a history of familial obesity a significant fall in HLA A2 antigen (p <.03) as compared to controls. 3)All obese patients evidenced a highly significant increase in HLA -A and -B blanks as compared to controls, the increase being higher for locus A (chi square=47.83, p<<.0001) than for locus B (chi square=9.20, p <.003). This seems to support the hypothesis that at least in a number of patients hereditary predisposition plays an important role in the aetiology of obesity and to indicate that such predisposition involves genes controlled by the HLA chromosomic region. The higher frequency of blanks in obese subjects might be connected with a diminished phenotypic expression of HLA antigens or with the presence in the serum of obese patients of a HLA antigens masking factor.

Water buffalo (Bubalus bubalus Arnee) allotypes: identification of a multiple allelic system.

This paper describes two allotypes of water buffalo controlled by two codominant allelic genes. The third allele is a null allele and behaves as a recessive one. The two detectable serum antigens are termed A1 and A2 and the third one (as yet undetectable) A0. The A1 antigen was recovered in the third peak and A2 antigen in the first peak following gel filtration through Sephadex G-200. The A1 antigen is common to water buffalo and cattle; the frequency of the corresponding gene (A1) was the same in both species.

HUMORAL AND CELLULAR IMMUNE RESPONSES TO STREPTOCOCCI, INFLUENZA AND OTHER ANTIGENS IN AUSTRALIAN ABORIGINAL SCHOOL CHILDREN

SYNOPSIS Aboriginal school children with elevated erythrocyte sedimentation rates were selected, and associated features of growth retardation, hyperimmunoglobulinaemia, high streptococcal carrier rates and antibody levels, and high loads of bowel parasite infestation, noted previously, were confirmed. Medical records showed these children to have had significant growth retardation in infancy, which suggested an association with previous protein-calorie malnutrition. Antibody responses of these children to influenza vaccine were significantly poorer than controls, both in the magnitude of antibody rise and the proportion of children showing significant rises in titre. Some improvement in antibody response followed treatment of chronic streptococcal infection, or of bowel parasites. Cell-mediated immune responses, as measured by lymphocyte transformation in vitro in response to specific antigens streptolysin O, tetanus toxoid, non-specific mitogens PHA and streptolysin S, and also by delayed hypersensitivity reactions to monilia antigen on skin testing, were diminished in children with high ESR, relative to controls. However, enhanced cellular responses in the abnormal children occurred to influenza A2 antigen, and to streptococcal group A polysaccharide, the latter possibly explaining chronic low-grade tissue damage noted previously in these children. These findings are discussed in relation to resistance to infection and the pathogenesis of rheumatic fever, and a possible basis suggested in acquired change in function of the thymus, perhaps related to protein-calorie malnutrition in infancy.

Quantitative measurements concerning A and B antigen sites.

SummaryUsing 125I‐labelled anti‐A and anti‐B, the number of A and B antigen sites per red cell for samples obtained from adults of different phenotypes was estimated to be: on A1 cells, 0.81—1.17×106; on A1B cells, 0.46—0.85×105; on A2 cells, 0.24—0.29×106; on A2B cells, 0.12×106. The number of sites on A1 cells obtained from cord blood was 0.25—0.37×106, and on the single example of A2 cord cells were 0.14×108 sites. The number of B sites on adult cells were as follows: on B cells, 0.61—0.83×106; on A1B cells, 0.31—0.56×106 sites.The equilibrium constants and the rates of dissociation of the reaction between anti‐A and A1 and A2 cells were also determined. The value of the equilibrium constant was approximately three times as great and the rate of dissociation three times as slow with A1 cells compared to A2 cells. This is consistant with the view that theere is a small difference in the molecular structure between the A1 and A2 antigen.