Although not studied as extensively as the genes encoded by the major histocompatibility complex (MHC), control of immune activity via genes not linked to the MHC are also known. One especially interesting region in the murine model is composed of numerous loci which are linked to agouti in the fifth linkage group of chromosome 2. To date, several loci have been described: two minor histocompatibility antigen (MHAG) loci, H-3 and H13, map to the left of agouti, both of these loci are described to be polymorphic; an IrGENE (Ir-2) maps between H-3 and H-13 which controls the amount of agglutinating antibody produced to the Ea-1 erythrocyte antigen; acquired resistance to the parasite, Leishmania donovani, is controlled by a gene(s) in the Ir-2 region; an Ir-gene controls the generation of cytotoxic lymphocytes specific for the H-Y antigen; gene(s) are present which control Ly-4 Ly-mll and beta-microglobulin, all of which are cell surface antigens [Ly-mll is reported to be the same as beta-2-microglobulin]; and a gene, Pgp-2, controls a cell surface glycoprotein of macrophages and other phagocytes. In addition, we presented evidence for the existence of another gene that is linked to agouti. This gene maps to the left of H-13 and controls a product which induced CTL as well as served as an antigen for CTLs whose activity was H-2 restricted. Based on skin graft studies with F1 animals, our evidence suggests that this new gene most likely controls a MHAG. Preliminary evidence indicates that there is a second MHAG locus closely linked to H-3. Even though numerous genes have been found associated with H-3, only Ir-2, Pgp-2, the gene controlling L. donovani resistance and the MHAG loci that we defined have been shown to be distinct from H-3. Whether the others are the same as H-3 or the new MHAG loci or are closely linked genes have not been established. Because of the potential biological implications both of a cluster of immunogenetic genes mapping distinct from the MHC, and the MHAG loci occur as complexes of very closely linked multiple loci, it is imperative to study H-3 in a manner similar to that devoted to the MHC. It is the aim of thos proposal, therefore, to: 1. Evaluate and define the genetic make-up of the loci associated with H-3 in the fifth linkage group of chromosome 2; and 2. Derive new congenic strains that will differ from B10 at fewer MHAG loci than those that are presently available.
