T-cell receptor genes in autoimmunity.
T cells are primary participants in the pathogenesis of the MHC-dependent autoimmune diseases, and therefore, evidence for association of TCR V-gene repertoires with such disorders has been actively sought. With very few exceptions, no clear-cut evidence for correlation of particular RFLP-defined V-C-region genomic polymorphisms with autoimmune disease predisposition has thus far been demonstrated. With regard to TCR V-gene repertoires engaged in responses to autoantigens, restricted use of certain V beta and V alpha genes in response to myelin basic protein has been documented in animal models. In many spontaneous and experimentally induced animal and human autoimmune diseases, however, the picture is far from clear. Although dominance of certain TCR V genes has been noted, the clonal restrictions are not absolute; they differ from one study to another and from one patient to another. Such variations may be caused by MHC allele-dependent determinant selection mechanisms, secondary T-cell infiltrates in inflammatory sites, different patient populations and stages of disease, or the involvement of different pathogens that, nevertheless, lead to the same clinical entity. Overall, the results indicate that efforts to intervene therapeutically in autoimmune diseases by vaccination with modified T-cell clones, V region-synthetic peptides, or TCR blocking analogues may not be easily applicable. Further studies on the characterization of the specific antigens involved in autoimmune disease pathogenesis is required in order to accurately address the issue of TCR utilization in autoimmune diseases.
Theofilopoulos
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AN
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Balderas
R S
RS
Baccala
R
R
Kono
D H
DH
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity; D015870:Gene Expression; D005796:Genes; D006801:Humans; D007108:Immune Tolerance; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell