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Results for “HLA-B7 Antigen”

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At least 19 recordsLinked to original sources

Genetics of cell-mediated lympholysis in man.

Cell-mediated lympholysis (CML) was studied in a family containing two siblings in who genetic recombinaiton had occurred in the HLA comples. In one sibling, recombination occurred between the HLA-A locus and the HLA-B locus. In the second sibling recombination occurred between the HLA-B locus and the HLA-D locus. Strong CML activity was generated in mixed lymphocyte cultures (MLC) when stimulator and responder cells differed in HLA-A, B, and D antigens. MLC involving HLA-D differences alone did not generate CML. Weak, but definite CML activity was generated during MLC with cells differing at HLA-A and HLA-B but sharing HLA-D. HLA-B antigens were good targets for lysis in all combinations studied. HLA-A antigens were poor targets in some but not in all combinations. However, combinations where HLA-A antigens seemed to be good targets could have involved HLA-B differences due to polymorphism of HLA-B7 antigens each inherited from a different parent. HLA-D antigens did not serve as targets for lysis. In three cell experiments, excellent CML activity was generated when responder cells were stimulated by HLA-D antigens and by HLA-A and B antigens present on separate stimulator cells.

Adult

HLA-B specificities and w4, w6 specificities are on the same polypeptide.

The human alloantigenic specificities w4 and w6, which are products of a diallelic system genetically associated with the HLA-B locus, have been solubilized by papain digestion of membranes from the lymphoblastoid cell line, RPMI 4265. The w4 and w6 specificities copurified with the HLA-B locus products, HLA-B7 and HLA-B12. Sequential immunoprecipitation experiments were performed using alloantisera to HLA-B7, HLA-B12, w4 and w6, and a purified HLA-B7, B12, w4, w6 antigen pool labeled with 125I-Bolton-Hunter reagent. These experiments demonstrated directly that HLA-B7 and w6, which are genetically associated with each other, are different antigenic determinants on the same molecule, while HLA-B12 and w4, also genetically associated, are distinct antigenic determinants on a second molecule. Arguments are presented which suggest that the HLA-B determinants and w4, w6 determinants are in fact on the same polypeptide, and the genetic implications of the findings are discussed.

Alleles

Frequency of HLA antigens in chronic myelocytic leukemia.

Histocompatibility antigen (HLA) phenotypes of 34 patients with Ph1+ chronic myelogenous leukemia (CML) were evaluated for association with HLA antigens. Two control populations were compared to the CML patients: 142 normal volunteer platelet donors, and 160 normal donors of granulocyte transfusions. HLA typing was done by lymphocyte microcytotoxicity tests for nine antigens on sublocus A and 15 antigens on sublocus B. HLA-B7 and HLA-B12 were decreased in CML patients compared to both platelet and granulocyte donors. There was increased frequency of HLA-A3 in patients (41%) as compared to controls (25% and 33%); HLA-B5 - patients = 20%; controls 8% and 6%; and HLA-BW17 - patients = 17%; controls = 6% and 3% (P = 0.01). Median survival was 24+ months and independent of HLA. HLA-B5 and HLA-BW17 were significantly increased in patients with CML compared to two normal control populations. No increase in HLA-B8 was seen. Decreased frequency of HLA-B7 and B12 was noted. The significance of these differences is being evaluated.

Chromosome Aberrations

HLA antigens in pernicious anaemia.

The increased frequency of HLA-B7 alone and HLA-A3/B7 together, in the same patient, has been confirmed in pernicious anaemia. There is no increase prevalence of HLA-A3 alone. No association has been found between the presence of serum intrinsic factor type 1 antibody and HLA-A3 or HLA-B7.

Anemia, Pernicious

Cross-reactions of HLA antibodies: VII. Rate of sensitization and serological specificity.

Varying the sensitization time of the complement-dependent antibody mediated cytotoxicity test, while carefully controlling other test conditions, has enabled us to characterize the subtle reactivities of several broadly reactive sera. In particular, we can discriminate between classes of cells, e.g., HLA-B7 from B27; subclasses cells, e.g., Bw51 from Bw52; and cells carrying new antigens, e.g., Ao79. This manipulation of the cytotoxicity test is discussed in view of its usefulness in separating primary from cross-reactive specificities and in detecting new specificities.

Adult

Public antigenic determinant on a family of HLA-B molecules.

Serologic cross-reactivity among allelic gene products commonly occurs in the HLA complex, but the molecular basis of these serologic phenomena is incompletely characterized. Because of strong cross-reactivity among antigens comprising the B7 cross-reactive group (i.e., HLA-B7, Bw22, B27, B40, and Bw42) and because of the association of several antigens of this group with spondyloarthropathies, we initiated a study of the chemical basis of cross-reactivity among this group of antigens. Using classic serologic procedures, 125I-Protein A binding assay, and chemical immunoprecipitation techniques, we have defined a new antigenic determinant, tentatively designated "X", which is present on certain HLA-B molecules. By a series of sequential immunoprecipitation experiments, X was shown to be a "public" antigenic determinant distinct from the "private" determinants B7, Bw22, B27, and B40, but present on the same 44,000-dalton glycoprotein molecules. The implications of this finding regarding disease predisposition and HLA typing as a diagnostic aid are discussed.

Arthritis, Reactive

Comparison of amino acid sequences of two human histocompatibility antigens, HLA-A2 and HLA-B7: location of putative alloantigenic sites.

The complete amino acid sequence for papain-solubilized HLA-B7 heavy chain is compared with the partial sequences of HLA-A2 and H-2Kb heavy chains. Although these molecules are highly conserved (i.e., 80% homology in comparing HLA-B7 with HLA-A2; 72% and 74% homology in comparing H-2Kb with HLA-A2 and HLA-B7, respectively), two stretches of greater variability are observed. These clusters of variability are discussed in terms of their possible involvement in the alloantigenic determinant(s) characteristic of these highly polymorphic membrane antigens.

Amino Acid Sequence

Heavy chain of HLA-A and HLA-B antigens is conformationally labile: a possible role for beta 2-microglobulin.

The three-dimensional organization of HLA antigens has been investigated by spectroscopic and immunochemical techniques. Measurement of the circular dichroism shows that in papain-solubilized HLA the heavy chain as well as the previously studied light chain (beta 2-microglobulin) consists predominantly of beta-pleated sheet structures. When heavy chain is separated from the light chain under denaturing conditions and is allowed to renature, about 50% of the beta structure is lost, concomitantly with most of the alloantigenic activity. Analysis of the two acid-cleaved fragments of HLA-B7 heavy chain shows that beta structure is preferentially lost from the COOH-terminal region of the heavy chain. Exposure to denaturants per se does not inevitably result in irreversible loss of antigenic activity. However, recovery of antigenic properties does seem to depend on reassociation of the two chains. The results reported here provide further evidence for (i) the similarity of HLA antigens and immunoglobulins at the three-dimensional level and (ii) two distinct and physiologically important conformations of the HLA heavy chain, depending upon whether it is associated with the light chain.

Beta-Globulins

B-lymphocyte alloantigens associated with multiple sclerosis.

6 B-lymphocyte alloantigens have been provisionally identified with lymphocytotoxic antisera reacting, after absorption, specifically with B but not T cells. 3 of these antigens appear to form part of an allelic series. The frequency of HLA and B-lymphocyte antigens was then studied in 59 patients with multiple sclerosis (M.S.). 1 of the B-cell antigens, BT 101, was found in 49 out of 59 patients (83%), compared with 10 out of 30 normal individuals (33%), giving a relative risk of 9-8 times to the association. 2 other B-cell alloantigens and HLA-B7 showed lesser but significant positive associations with M.S. Apart from providing possible clues to the pathogenesis of M.S., the association between BT 101 and M.S. may allow screening for susceptible individuals who are thought to be at special risk.

Adolescent

HLA-typing and lymphocyte population studies in patients with multiple sclerosis.

Compared to a control population, the frequency of HLA-B7 was increased in a group of 46 patients with a chronic progressive form of multiple sclerosis (MS) (RR = 2.9, P = 0.01). Significance of the association was lost after correction for first order error. Results on serotyping for "B-cell DW2" antigen are suggestive of an increased frequency of this antigen in chronic progressive MS patients (RR = 2.9, P = 0.01). The percentage of T-cells (E-rosette forming lymphocytes) in MS patients was lower (mean 46 +/- 17%, n = 34) than in a control group (mean 62 +/- 10%, n = 90). Only 5 of the 40 patients had high B-lymphocyte percentages, whereas no difference in B-cell counts was observed between the total group of patients and the control group. The T- and B-lymphocyte ratio in the MS patients was lower than in the control group. The 7 patients, with the lowest T/B-cell ratio were negative for "B-cell DW2" antigen. In 3 patients, the sum of T plus B-lymphocytes was far lower than 90%. At least 4 patients had in their serum antibodies against autologous lymphocytes as found by immunofluorescence tests. No correlation could be found between these serological and immunological data and clinical data on progression of the disease, the IgG in CSF and improvement after immunosuppressive treatment.

Antigens

A suppressor T cell in the human mixed lymphocyte reaction.

Lymphocytes from an HLA-B7 DW2 homozygous multiparous woman, J.H., failed to respond in the mixed lymphocyte reaction to lymphocytes from her DW1 homozygous husband, W.H., and certain other homozygous typing cells. J.H. lymphocytes could suppress the response of HLA matched responders to W.H. This effect was shown to be radiosensitive and due to a T cell. The suppressor cell showed antigen specificity.

Cells, Cultured

Strong linkage disequilibrium between HLA-Dw2 and and BfS in multiple sclerosis and in the normal population.

An increased frequency of the S allele of Properdin factor B (BfS) was found amongst 162 patients with multiple sclerosis (MS) compared with 470 normal controls. This increase was shown to be due to a strong linkage disequilibrium (LD) between BfS and HLA-Dw2 in 77 patients typed for both systems (delta = 3.84%, P = .0002). The same LD was demonstrated amongst 100 normal controls (delta = 2.24%, P = .0049) and 31 patients with idiopathic demyelination of the peripheral nervous system (IDPN). A total of 70 haplotypes with HLA-Dw2 were encountered (40 MS, seven IDPN and 23 normal controls) and all contained BfS. In the MS patient group, a much weaker association was noted between BfS and HLA-B7 suggesting either that the Bf locus is musch closer to the HLA-D than the HLA-B locus or (and) that HLA-D and Bf products selectively interact (perhaps on the surface of B lymphocytes) with evolutionary advantage or disadvantage resulting from certain allelic combinations. Strong associations between BfS1 and HLA-Bw21 (P = .0000) and BfF1 and HLA-B18 (P = .0001), both previously reported, were confirmed in the current study. No increase in the frequency of a glyoxalase (GLO) allele was found amongst the MS patients and no LD was encountered between HLA-Dw2 and a GLO allele. The possibility that the HLA-Dw2, BfS disequilibrium has resulted from a selective advantage conferred on the general community but at the expense of increasing susceptibility to MS should be considered.

Chromosome Mapping

HLA antigens in a Scottish psoriatic population.

Sixty-one patients in the Dundee area suffering from psoriasis were typed for HLA-A and HLA-B antigens. On the basis of the typing results, the patients were divided into three groups, and studied with respect to sex, age of onset and familial incidence of the disease. The frequency of HLA-A1 appeared to be increased and HLA-B7 decreased but HLA-B13 and HLA-B17 were highly significantly increased (P less than 10(-6) and P less than 10(-10) respectively) in the psoriatic group compared to 204 controls. Of particular interest was a highly significant association of HLA-A1 with HLA-B17 in psoriatic patients. Family studies showed HLA-B17 to be a useful genetic marker for psoriasis in the families of B17 positive patients. Considerations of age of onset, familial incidence and typing data suggest that there is heterogeneity of genetic susceptibility to psoriasis and that one probable mechanism is the dominant inheritance of a "disease allele" in linkage disequilibrium with the allele coding for HLA-B17.

Chromosome Mapping

Cellular immunity to encephalitogenic protein in multiple sclerosis. Correlations with other laboratory characteristics at different disease courses.

A very suggestive, although non-significant, correlation was found between cellular immunity to encephalitogenic protein in multiple sclerosis and the genetic marker HLA-B7 in patients with no disease activity during at least the past 5 years and in those with a chronic progressive disease course during recent years, but not in patients studied longitudinally after a relapse. Only the latter group showed a significant correlation with parameters indicating intrathecal synthesis of immunoglobulin. No correlation was demonstrable with a parameter indicating intrathecal synthesis of measles antibodies.

Antibodies, Viral

Detergent solubilization, purification, and separation of specificities of HLA antigens from a cultured human lymphoblastoid line, RPMI 4265.

HLA antigens have been purified to homogeneity after detergent solubilization from RPMI 4265, a human lymphoblastoid line. The inhibition of cytotoxicity assay for HLA antigen was modified, using preincubation with bovine serum albumin of antigen samples containing detergent to prevent lysis of target cells by detergent. Solubilization was tested with many types of detergents. A polyethyleneglycol oleyl ether nonionic detergent mixture, Brij 99:Brij 97 (2:1) was selected for solubilization, since it selectively solubilized HLA antigens, had a low absorbance at 280 nm and was uncharded. HLA antigens were then purified by Lens culinaris lectin affinity chromatography and Bio-Gel A-5m filtration. The antigen specifity HLA-A2 was separated from specificities HLA-B7,12 by isoelectric focusing. Purified HLA antigens contained a subunit of Mr=44,000 with NH2-terminal glycine, and a subunit of Mr=12,000, beta2-microglobulin, with NH2-terminal isoleucine.

Amino Acids