Self-tolerance alters T-cell receptor expression in an antigen-specific MHC restricted immune response.
The influence of major histocompatibility complex (MHC) gene products on the T-lymphocyte alpha beta receptor (TCR) repertoire is well documented, but how specificity is also generated for a diverse array of foreign peptide antigens is unknown. One proposed mechanism is that the TCR repertoire is selected by the recognition of processed self-antigens bound to MHC molecules. Here, we examine the influence of non-MHC-encoded self-antigens on the TCR repertoire expressed in an antigen-specific immune response. Most pigeon cytochrome c-specific, Ek alpha Ek beta (Ek) Ia-restricted T cells from B10.A mice express a product of the V alpha 11 gene family in association with a V beta 3 gene-encoded protein. We therefore examined V alpha 11 and V beta 3 gene expression in cytochrome c-specific T-cell lines derived from various mouse strains with different non-MHC genetic backgrounds. T cells from several strains failed to express any V beta 3 due to tolerance induced by Mlsc-encoded self-antigens. Variable levels of V alpha 11 messenger RNA (mRNA) were expressed by antigen-specific T cells from all the strains. In one strain V beta 3 was expressed in the relative absence of V alpha 11. These results directly demonstrate that self-tolerance alters TCR gene usage in the immune response to a foreign antigen, and indicate that TCR V alpha and V beta proteins may, in part, be independently selected.
Fry
A M
AM
Division of Biochemistry and Biophysics, Food and Drug Administration, Bethesda, Maryland 20892.
Matis
L A
LA
D000818:Animals; D000941:Antigens / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D010856:Columbidae / Q000276:immunology; D003574:Cytochrome c Group / Q000276:immunology; D005786:Gene Expression Regulation; D007108:Immune Tolerance; D008285:Major Histocompatibility Complex; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D001324:Autoantigens; D003574:Cytochrome c Group; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell