These investigations promise to enhance research activity at CCSU by providing students with a variety of defined projects focused on the further characterization of two unusual minor histocompatibility (H) models in mice: H-hix and H.mshi. H-hix. for histoincompatibilitv on the X chromosome. Classical analysis of X-linked minor transplantation barriers has suggested that a single, polymorphic gene (Hxa) is responsible for generating skin-graft incompatibility among different inbred strains of mice. Our recent efforts to further characterize the X-linked incompatibility previously described for strains C57BL/6 and BALB/c has shown instead that this allograft rejection is mediated by at least two distinct antigens that are likely the products of more than one gene. Thus, we propose that these two strains encode different haplotypes of antigen-encoding loci (called H-hixb and H-hixC), rather than different alleles of a single Hxa locus. Furthermore, we hypothesize that other strain combinations may identity additional, distinct sets of X-linked antigen-encoding loci. Here we propose to genetically map the H-hixb, H-hixc disparity--as well as other H-hix haplotype pairs that we aim to identity--to test two current models regarding minor histocompatibility locus structure, and to provide a foundation for the future cloning and molecular analysis of each distinct H-hix component. H-mshi for histoincompatibility associated with the mshi mutation. The male sterility and histoincompatibility mutation (mshi) was initially detected on a BALB/c genetic background as a spontaneous antigen-loss type H variant that rejected wild-type skin grafts. Our previous work with this variant has shown that H-mshi may exemplify a new type of minor histocompatibility locus that has resulted from the mutation of a single, highly conserved gene; and mediates an unusual, cytotoxic-T-lymphocyte-independent rejection mechanism. In addition, we have genetically mapped mshi to a small region that includes fewer than 20 genes. Here we propose to screen these candidates to identify the gene disrupted by the mshi mutation. To confirm this molecular assignment and to allow the complete functional and structural dissection of H-mshi, we also propose to isolate a T-helper cell clone and serum antibodies specifically reactive to the H-mshi+ antigens.
NIH ExPorter
NIH ExPorter