Antigen-presenting Cell-expressed Specificity of T Cell Antigen Recognition Identification of a Site of Interaction and Its Relationship to Ir Genes Ettore Appella

Ia region gene products have long been postulated to be antigen-binding (recognition) molecules (1); in particular, one set of hypotheses suggests that they are participants along with a T cell product in the antigen-binding complex (2, 3). It has recently been observed that certain T cell clones will react to antigen in association with two different major histocompatibility complex (MHC) 1 haplotypes, but in doing so these clones display different antigen specificities (4, 5). Such results have been interpreted as support for the above hypothesis. In the present work we have subjected the postulate to a further test by attempting to identify the site on a peptide antigen that interacts with the Ia molecule (i.e. controls the specificity changes that accompany the changes of MHC type) and the presumably different site that interacts with the T cell (i.e. contributes to immune memory). In our initial studies, the nominal antigens were peptides consisting of residues 81-104 or 81-103 of the cytochrome c from pigeon or moth, respectively. B10.A mice immunized with low doses of either the pigeon 81-104 or moth 81-103 responded to both moth and pigeon fragments. However, B10.A(5R) mice immunized with low doses of pigeon fragment showed no response at all. When B10.A(5R) mice were immunized with large doses of moth fragment a strong response was seen, but this immune response showed no cross-reactivity with the pigeon peptide. IL2-secreting T cell hybridomas from a moth-primed B10.A(5R) or a pigeon-primed B10.A mouse were prepared and tested with antigen-presenting cells (APC) of these two strains. It was found that the T cell hybridomas from either strain responded to antigen associated with either B 10.A or B10.A(5R) APC but to no others (5). Surprisingly, the specificity pattern was determined not by the MHC genes of the T cell hybridoma but by those of the

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