Allelic exclusion of alpha chains in TCRs. 1994

D Mason
MRC Cellular Immunology Unit, Sir William Dunn School of Pathology, Oxford, UK.

Although the beta chains of alpha beta+ T cells exhibit allelic exclusion it has recently been shown that approximately 20-30% of such cells express both alpha chain alleles on their surface. Potentially these cells have dual specificity, and it has been suggested that they may play a role in autoimmunity and alloreactivity. The analysis presented in this paper examines critically the possibility that the observed violation of allelic exclusion of alpha chain expression arises as a natural consequence of alpha chain rearrangement and intrathymic positive selection. It is concluded that, subject to certain identified conditions being satisfied, the observed frequency of T cells expressing two alpha chains is compatible with such a mechanism. However, it is an essential assumption of the theory that, of the two alpha beta chain complexes on these cells, only one mediates positive selection. It follows that to what extent both receptors are actually functional depends on whether an alpha beta chain complex that has failed to satisfy the criterion of positive selection can mediate antigen recognition in the periphery. In principle the answer to this question may be different if one is considering autoreactivity or alloreactivity. Finally, attention is drawn to the apparent discrepancy between the frequency of peripheral T cells expressing two alpha chains and the failure to find T cell clones of this phenotype. Possible explanations are discussed.

UI MeSH Term Description Entries
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D011947 Receptors, Antigen, B-Cell IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment. Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000483 Alleles Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product. Allelomorphs,Allele,Allelomorph
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D015332 Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor Ordered rearrangement of T-cell variable gene regions coding for the alpha-chain of antigen receptors. T-Cell Antigen Receptor alpha-Chain Gene Rearrangement,T-Lymphocyte Antigen Receptor alpha-Chain Gene Rearrangement,Gene Rearrangement, alpha-Chain T Cell Antigen Receptor,T Cell alpha-Chain Gene Rearrangement,T Lymphocyte alpha-Chain Gene Rearrangement,Gene Rearrangement, alpha Chain T Cell Antigen Receptor,T Cell Antigen Receptor alpha Chain Gene Rearrangement,T Cell alpha Chain Gene Rearrangement,T Lymphocyte Antigen Receptor alpha Chain Gene Rearrangement,T Lymphocyte alpha Chain Gene Rearrangement
D015551 Autoimmunity Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES. Autoimmune Response,Autoimmune Responses,Autoimmunities
D016693 Receptors, Antigen, T-Cell, alpha-beta T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules. Antigen Receptors, T-Cell, alpha-beta,T-Cell Receptors alpha-Chain,T-Cell Receptors beta-Chain,T-Cell Receptors, alpha-beta,TcR alpha-beta,Antigen T Cell Receptor, alpha Chain,Antigen T Cell Receptor, beta Chain,Receptors, Antigen, T Cell, alpha beta,T Cell Receptors, alpha beta,T-Cell Receptor alpha-Chain,T-Cell Receptor beta-Chain,T-Cell Receptor, alpha-beta,T Cell Receptor alpha Chain,T Cell Receptor beta Chain,T Cell Receptor, alpha beta,T Cell Receptors alpha Chain,T Cell Receptors beta Chain,TcR alpha beta,alpha-Chain, T-Cell Receptor,alpha-Chain, T-Cell Receptors,alpha-beta T-Cell Receptor,alpha-beta T-Cell Receptors,alpha-beta, TcR,beta-Chain, T-Cell Receptor,beta-Chain, T-Cell Receptors
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