Genetic Control of the Antibody Response to Trinitrophenylated - Polysaccharides.

Abstract

Analysis of the primary in vitro antibody response to the type 2 antigen TNP-Ficoll in congenic-recombinant mouse strains demonstrated that this response was regulated by two loci, one in the I-A subregion and a second in or to the right of the I-E subregion of the MHC. The high response of certain (low responder x low responder)F(,1) hybrids demonstrated that these loci could complement in the trans configuration. Further analysis of the B10.S(7R) and B10.A(2R) strains indicated that the right h and locus of control mapped between the H-2S and H-2D regions of the major histocompatibility complex. Different responses in three strains derived from similar parents (B10.BAR6, B10.BAR10, B10.BAR11) with crossover events between the S and D regions defined the right h and locus in the same set of haplotypes. The response to TNP-Ficoll could be blocked at the macrophage level with antiserum directed against either locus of control, which confirmed the dual gene control. Absorption of class I specific antibodies from alloantiserum directed against the right h and locus did not remove antibodies which block the TNP-Ficoll response. Similarly, monoclonal anti-H-2D('b) antibodies did not block the response. A monoclonal antibody (48-21.7) recognizing the right h and specificity was prepared and significantly blocked the response to TNP-Ficoll in the b haplotype. 48-21.7 had no effect on inappropriate haplotype responses to TNP-Ficoll or responses to other T-dependent antigens. Cytotoxic tests with 48-21.7 indicated that this antibody recognized a unique specificity in the b haplotype between E(,(beta)) and the D region, and not an auto-reactive, background, or class I determinant. These experiments also demonstrated that the high responder determinants of the b and s haplotypes were not cross-reactive. Finally, the monoclonal antibody 48-21.7 immunoprecipitated a product of approximately 40,000 molecular weight which migrated slightly faster than the class I product recognized by the H-2D('b) specific monoclonal antibody B22/249. Sequential immunoprecipitation analysis of 48-21.7 and B22/249 indicated that these monoclonal antibodies precipitated two distinct products.