Cell Receptor Beta Chain Locus Research Articles

Analysis of Germline and Expressed T Cell Receptor Variable Region Genes in Crohn's Disease

A possible role of the T cell receptor genes in the pathogenesis of Crohn's disease was investigated by 1) comparison of restriction fragment length polymorphisms at the T cell receptor beta chain locus in 64 Crohn's patients and 64 normal controls; 2) semi-quantitative polymerase chain reaction analysis of T cell receptor beta and alpha chain variable region gene expression by lamina propria lymphocytes from resected segments of diseased terminal ileum. We found no association between any of the restriction fragment length polymorphisms and Crohn's disease using polymorphic markers spanning the T cell receptor beta chain locus. Analysis of T cell receptor V beta and V alpha gene expression showed that expression of T cell receptor V region families in terminal ileum lymphocytes from patients with active Crohn's disease was indistinguishable from the lymphocytes found in normal terminal ileum. These data fail to support susceptibility to Crohn's disease being associated with the T cell beta chain antigen receptor genotype. No restricted or dominant T cell receptor variable region gene expression was found in Crohn's disease tissue, compared to normal terminal ileum.

Genetic differences in the T cell receptor alleles of LEW rats and their encephalomyelitis‐resistant derivative, LER, and their impact on the inheritance of EAE resistance

Experimental allergic encephalomyelitis (EAE) is an animal model for the human disease, multiple sclerosis. The LEW rat strain is very susceptible to induction of EAE, whereas the closely related, major histocompatibility complex (MHC)-identical, inbred strain LER is resistant. In this report, the two rat strains have been compared for differences at a number of immunologically relevant loci by restriction fragment length analysis and by nucleotide sequencing. A major difference between the two strains was discovered at the T cell receptor beta chain locus (TcR beta). Both variable (V beta 8) and constant (C beta 1) region elements of TcR beta showed allelic variation between LEW and LER. The known genetic influences in rat models of autoimmunity are currently limited to those encoded by the rat MHC, RT-1. In this study we report our characterization of the allelic differences in TcR beta chains between two rats which differ in their susceptibility to induced EAE, with the goal of understanding the role played by these allelic forms of TcR in the pathogenesis of EAE. The importance of the TcR beta allelic difference in resistance or susceptibility to EAE was assessed in a study of backcross rats scored for both EAE and for the novel LER TcR beta allele. We found that the TcR beta allele from the susceptible strain was present in three out of four susceptible rats, suggesting that it is an important, but not the only, genetic factor in EAE. Supporting this conclusion were the observations that 12 of 13 rats with homozygous LER-derived TCR beta alleles were resistant to EAE.

T cell receptor gene rearrangements define a monoclonal T cell proliferation in patients with T cell lymphocytosis and cytopenia

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic “classic” T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.

T Cell Receptor Gene Rearrangements Define a Monoclonal T Cell Proliferation in Patients With T Cell Lymphocytosis and Cytopenia

We have used probes from the T cell receptor beta and gamma chain loci to investigate the clonality of T lymphocytes in eight patients with T cell lymphocytosis and cytopenia (TCLC). This syndrome, which is strongly associated with rheumatoid arthritis, is characterized by peripheral blood and bone marrow lymphocytosis and neutropenia, red cell aplasia, or both. By means of T cell monoclonal antibodies and flow cytometry, T lymphocytes from patients with this syndrome have been shown to have characteristic immunologic features. Investigators have disagreed as to whether the syndrome represents a T cell malignancy or a more benign immunologic disorder. DNA from five of five patients with symptomatic "classic" T cell lymphocytosis with cytopenia demonstrated unique rearrangements of the T cell receptor beta chain locus, whereas neither of two patients with atypical features showed rearrangement. In addition, we found evidence for gamma chain rearrangement in those DNAs with clonal beta chain rearrangement. We thus postulate that the classic form of this syndrome is associated with a monoclonal proliferation of T cells. Its potential relationship to T cell chronic lymphocytic leukemia is discussed.

Detection of a frequent restriction fragment length polymorphism in the human T cell antigen receptor beta chain locus. A potential diagnostic tool.

Abnormal T cell function is a feature of a spectrum of inherited and acquired diseases. We have detected a frequent restriction fragment length polymorphism in the human T cell antigen receptor beta-chain locus that may aid in the analysis of these disorders. A study of a panel of 18 normal individuals, testing for the presence of the polymorphism, showed it to account for 36% of the alleles in that group. In view of the fact that the T cell receptor beta-chain locus has been mapped to chromosome 7, and that the disease ataxia telangiectasia (AT) is associated both with abnormal T cell function and with chromosomal abnormalities of the same region of chromosome 7, we investigated the possibility that the polymorphism could demonstrate linkage of the T cell receptor locus to the gene for that disease. We demonstrated that the mutation causing AT did not lie within the beta-chain locus itself, and that there was preliminary evidence that the two loci were not closely linked. This polymorphism may provide a useful tool for the study of other genetic disorders associated with abnormalities of T cell function, as well as disorders associated with inherited or acquired abnormalities of chromosome 7.