We have previously described the B10.A pigeon cytochrome c-specific response in terms of clonal phenotypes and T-cell receptor (TcR) gene usage. All B10.A T-cell clones studied respond to antigen in association with syngeneic B10.A APCs and cross-react to antigen in association with one or two allogeneic variants of the I-E-encoded MHC molecules. In congenic strains of mice expressing these allogeneic MHC alleles [B10.A(5R) and B10.S(9R)], pigeon cytochrome c-specific T cells exhibit very similar MHC cross-reactivities. Our goal was to determine whether the same MHC cross-reactive T-cell clones were expressed in each appropriate strain, or whether each T-cell repertoire was unique. The results indicate that identical V alpha-J alpha and V beta-J beta combinations were expressed by the major pigeon cytochrome c-specific response phenotype in B10.A and B10.A(5R) mice. Previous functional data supports this overlap in expressed T-cell clones. B10.A and B10.S(9R) mice exhibit similar response phenotypes to pigeon cytochrome c but express distinctly different TcR genes. The results of these studies support the existence of at least two different mechanisms in determining MHC-linked immune response polymorphisms.