Separation of the Immune Response Genes for Ldh-B and Mopc-173.

Analysis of the immune responses of a panel of intra-I-region recombinant mouse strains to LDH-B and MOPC-173 demonstrated that B10.ASR7 and B10.BASR1 failed to mount T cell proliferative responses to MOPC-173 and LDH-B, respectively. Assignment of the E(,(beta)) allele in these two strains indicated that the recombinatorial events occurred within the A(,(alpha))A(,(beta)) gene duplex, suggesting that the immune response defects observed could be related to the site of recombination. Serological and functional examination of the I-A molecules expressed by these strains demonstrated I-A molecules with both I-A('k) and I-A('s) molecular determinants. Furthermore, the I-A('s) molecular determinants expressed by these strains were distinct, in that anti-I-A('s) serum absorbed with B10.ASR7 or B10.BASR1 spleen cells blocked only the MOPC-173 or LDH-B T cell proliferative response, respectively. To localize the level of the immune response defect in these strains, B10.ASR7 and B10.BASR1 macrophages were shown to be incapable of presenting MOPC-173 and LDH-B, respectively, to immune responder T cells. These results were confirmed using alloreactivity-depleted and (B10.ASR7 x B10.BASR1)F(,1) immune T cells. Failure of these strains to respond was shown not to be the result of T cell suppression, as cyclophosphamide and anti-Lyt2.2 plus complement treatments did not restore responsiveness. Furthermore, B10.BASR1 macrophages were incapable of educating naive responder T cells in vitro to LDH-B, however, naive nonresponder B10.BASR1 T cells could be educated by responder macrophages to LDH-B in vitro. These results suggest that the failure of B10.BASR1 to respond to LDH-B reflects a defect at the macrophage-T cell interaction level, perhaps due to the expression of unique I-A molecules. Finally, serological analysis using conventional antibodies and the monoclonal 59-88, obtained from a B10.S(8R) anti-B10.BASR1 fusion, suggested that the I-A molecules expressed by these strains contained I-A('k), I-A('s), as well as unique F(,1) I-A molecular determinants. Analysis of two dimensional PAGE techniques demonstrated that these recombinants express two I-A molecules with both I-A('k) and I-A('s) characteristics, perhaps generated by novel recominatorial events within the A(,(alpha))A(,(beta)) gene duplex which may result in the altered immune response patterns observed.PhDGeneticsUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/160138/1/8422241.pd