The influence of self-MHC and non-MHC antigens on the selection of an antigen-specific T cell receptor repertoire.
We have examined the influence of self-Ag on TCR expression and specificity in the immune response to the Ag pigeon cytochrome c. Previous work has shown that most Ek-restricted cytochrome c-specific T cells from B10 background mice express TCR alpha beta-heterodimers encoded by V beta 3 and V alpha 11 genes, but that T cells expressing V beta 3 proteins are eliminated due to self-tolerance in Mls-2a mouse strains. Thus, EK-restricted cytochrome c-specific T cells from Mls-2a mice fail to express any V beta 3. In the current study the influence of self-MHC and non-MHC Ag on TCR usage in the immune response to cytochrome c was further examined. First, it was demonstrated that the absence of V beta 3 expression in Mls-2a mice does not alter Ir gene function. Specifically, Mls-2a/Eb haplotype V beta 3- [C3H.SW x B10.A(5R)]F1 mice were high responders to cytochrome c despite the fact that previous structure function analyses have shown a very close correlation between Eb-restricted cytochrome c recognition and V beta 3 expression. This demonstration of the plasticity of TCR expression suggests that relatively few Ir gene defects result from tolerance induced by self-Ag. We also examined differences in V alpha 11 expression among cytochrome c-specific T cells from various H-2k haplotype mouse strains. In particular, the low level of expression of V alpha 11 in cytochrome c-specific T cells from C57BR (H-2k) mice was shown not to be due to self-tolerance. Rather, evidence for limited strain polymorphism of V alpha 11 genes, plus the fact that cytochrome c-specific T cells from F1 hybrids between H-2k, Mls-2b identical C57BR and B10.BR mice express high levels of V alpha 11, suggested the possibility that the variable V alpha 11 usage in the cytochrome c-specific responses of these two strains reflected differences in positive selection during ontogeny by non-MHC non-Mls self-Ag.
Fry
A M
AM
Division of Biochemistry and Biophysics, Food and Drug Administration, Bethesda, MD 20892.
Cotterman
M M
MM
Matis
L A
LA
D000818:Animals; D010856:Columbidae; D003574:Cytochrome c Group / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005802:Genes, MHC Class II; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007108:Immune Tolerance; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011110:Polymorphism, Genetic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity
D003574:Cytochrome c Group; D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; D007135:Immunoglobulin Variable Region; D011948:Receptors, Antigen, T-Cell