By using the intra-I region recombinant mouse strain B10.ASR7 (H-2(as3)), the immune response (Ir) genes for LDH-B and MOPC-173 were genetically and serologically separated, as assayed by T cell proliferation. Previous work demonstrated that H-2(s) and H-2b strains respond to LDH-B and MOPC-173 whereas H-2a and H-2(k) strains failed to respond due to haplotype-specific suppression of I-A(k) molecule-activated T helper cells by I-I(k) molecule-activated T suppressor cells. In the experiments reported here, B10.ASR7 mice, which lack I-E(k) expression, mounted a significant T cell proliferative response to LDH-B but not to MOPC-173. Separation of the Ia determinants used in restricting these two antigen responses was further confirmed when pretreatment of B10.S(9R) (A(β)(s)A(α)(s)E(α)(s)E(α)(k)) macrophages with A.TL anti-B10.HTT serum (anti-A(β)(s)E(β)(s)J(s)) adsorbed with B10.ASR7 spleen cells blocked the MOPC-173 response but not the LDH-B response. Unadsorbed serum blocked both antigen responses. The B10.ASR7 E(β) allele was determined to be s due to the ability of (A.TL x B10.ASR7)F1 hybrids to mount a T cell proliferative response to the terpolymer GLPhe. Monoclonal antibody blocking of the B10.ASR7 T cell proliferative response to LDH-B demonstrated that the Ia.2 and Ia.17, and not the Ia.15 epitopes are spatially related to the Ia epitopes involved in the restriction of the B10.ASR7 LDH-B T cell proliferative response. In addition, B10.ASR7 helper T cells generated in response to LDH-B were suppressed in a haplotype-specific manner by I-E(k) molecule-restricted suppressor T cells in that (A.TL x B10.ASR7)F1 hybrids failed to respond to LDH-B. This nonresponsiveness was eliminated by treatment with monoclonal antibodies directed against the I-E(k) molecule. These results suggest the possibility that the immune response defect in B10.ASR7 could be related to the site of recombination.
|Number of pages||5|
|Journal||Journal of Immunology|
|State||Published - 1984|