Cytochromes c have been used as antigens in a murine T-lymphocyte proliferation assay in order to characterize the nature of determinants whose recognition is under immune response (Ir) gene control. In the present studies, the T-cell proliferative response to pigeon cytochrome c was shown to be under the control of two complementing MHC-linked Ir genes in mice of the H-2a and H-2k haplotypes, while eight other haplotypes tested were low or non-responders. Complementation was demonstrated by showing that an F1 hybrid between two non-responder recombinant strains (H-2h4 and H-2i5) could respond to pigeon cytochrome c. The determinant on the cytochrome recognized in this immune response was located to the C-terminal portion of the molecule around residue 100. This was shown by the failure or success of closely related cytochromes to cross-stimulate T-cells immune to pigeon cytochrome.

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