The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation.

It is now clear that MHC-encoded molecules influence the immune response by their effects on T cell specificity. However, the mechanism(s) by which this occurs in an antigen-specific manner is not clear. Two broad categories of models have been proposed. One postulates that Ia molecules influence the T cell repertoire during ontogeny and that the clones of T cells capable of recognizing the antigen in association with the nonresponder Ia molecule are deleted or are never assembled. The other postulates that Ia molecules influence the immune response during T cell activation and that the clones of T cells capable of recognizing the antigen in association with the nonresponder Ia molecule are not stimulated because this Ia molecule does not bind or interact well with the antigen. Recent experiments by several laboratories have identified allogeneic T cell clones and populations capable of responding to an antigen in association with nonresponder Ia molecules. This result suggested that nonresponder Ia molecules are capable of interacting with antigen in a functional manner. Therefore it was inferred that Ir gene defects must lie in the T cell repertoire. However, we have recently discovered several mouse T cell clones whose characteristics suggest that this conclusion might not describe the complete picture. These clones have the unusual property of recognizing moth cytochrome c in association with either B10.A or B10.A(5R) Ia molecules, but they recognize pigeon cytochrome c only in associated with B10.A Ia molecules. Thus, the Ia-molecule-antigen interaction appears to be able to affect the fine specificity of the T cell activation process. Interestingly, the failure to respond to pigeon cytochrome c in association with B10.A(5R) Ia molecules correlates with the Ir gene control of the response to this antigen since the B10.A(5R) strain is a nonresponder to pigeon cytochrome c whereas the B10.A strain is a responder. The question we wished to address in this paper was whether the clones we had identified were representative of the T cell repertoires of both strains. If so, this would allow us to conclude that Ia molecule-antigen interactions during T cell activation could account for Ir gene control in certain situations. To answer the experimental question, we first examined several more T cell clones from [B10.A x B10.A(5R)]F1 and B10.A(5R) mice to solidify our previous findings. Then we turned to populations of T cells to determine if these findings could be generalized.(ABSTRACT TRUNCATED AT 400 WORDS)