XENOGENEIC RESPONSES INVITRO IN THE SYRIAN-HAMSTER, MESOCRICETUS-AURATUS .1. EVIDENCE FOR A NORMAL T-CELL REPERTOIRE

We have investigated the ability of Syrian hamster lymphocytes to generate cytotoxic responses against classical MHC molecules on xenogeneic cells. Our data show that hamster lymph node cells can be stimulated in an in vitro primary mixed lymphocyte culture by irradiated rat or mouse lymphoid cells to produce a substantial cytotoxic response assayed on Cr-51-labelled xenogeneic blasts. Using congenic recombinant rat and mouse targets, the specificity of the cytotoxic activity could be localized to genetic regions known to determine classical class I histocompatibility antigens in these two species. In addition, specific cytotoxicity could be demonstrated on transfectant target cells expressing only the relevant rat class I molecules, and specific cytotoxicity could be inhibited by a monoclonal antibody specific for a rat classical class I molecule. Elimination of B cells did not affect the ability of the responder population to generate xenogeneic cytotoxicity. In further experiments it was shown that hamster xenogeneic killers could distinguish between two subtly modified forms of a rat classical class I molecule essentially as efficiently as can allogeneic rat killers. Finally, lymph node cells from female hamsters primed in vivo with male hamster cells were able to generate weak but significant male-specific cytotoxicity after boosting in vitro. In sum, our experiments show that the general outline of the cytotoxic T cell repertoire of the Syrian hamster is conventional. These results suggest that monomorphic class I molecules expressed by the Syrian hamster probably function normally to direct the differentiation of its cytotoxic T cell repertoire.