Genetic control of the target structures recognized in hybrid resistance

Abstract

Hybrid resistance of lethally irradiated (C57BL/6 X DBA/2)F1 and (C57BL/10 X C3H)F1 hybrid mice to the engraftment of parental C57BL/6 or C57BL/10 bone marrow cells is controlled by the H-2-linked Hh-1 locus. This resistance can be specifically blocked or inhibited by the injection of irradiated spleen cells from lethally irradiated, marrow reconstituted donor mice of certain strains. By testing the ability of regenerating spleen cells from various donor strains to block the resistance, we studied the genetic requirements for the expression of putative cell-surface structures recognized in hybrid resistance to H-2b marrow cells. Strains of mice bearing informative intra-H-2 or H-2/Qa-Tla recombinant haplotypes provided evidence that the Hh-1 locus is located telomeric to the H-2S region complement loci and centromeric to the H-2D region class I locus in the H-2b chromosome. Two mutations that affect the class I H-2Db gene have no effect on Hh-1b gene expression. The H-2D region of the H-2s haplotype contains an allele of the Hh-1 locus indistinguishable from that of the H-2Db region, as judged by the phenotypes of relevant strains and F1 hybrids. Collectively these data indicate that the Hh-1 locus is distinct from the class I H-2D (L) locus in the H-2b or H-2s genome, and favor the view that the expression or recognition of the relevant determinants is not associated with class I gene products.

Class I H‐2Db determinants are not involved in hybrid resistance to parental H‐2b/Hh‐1b bone marrow allograft

“…Indeed, certain other properties of this resistance can now be explained more easily. These include the absence of codominant expression, apparent absence of a high degree of polymorphism in the Hh-1 locus [13], the lack of any effect of H-2Db mutations on the Hh-1 phenotype [13,271 and, indeed, the observation that NK cells or NK-like cells rather than T lymphocytes mediate the resistance. The nature of the putative cell surface structures that serve as target for HR and the way the Hh-1 genes control such structures are crucial questions that remain to be answered.…”

“…Studies using regenerating splenic hemopoietic cells as in vivo inhibitors show that the specificity of competition is controlled by the Hh-1 locus closely linked to the H-2D region [13]. Fig.…”

“…Since the H-2D locus allele in this haploty e may not be identical with the Db allele of the H-2b or H-2 -derived haplotypes, this apparent segregation could be viewed as an exception. Recent genetic studies indicate that this locus is, in fact, separable from class I H-2Db gene by a crossing-over on the centromeric side of the class I gene, converting the Hh-lb/H-2Db haplotype to a recombinant Hh-lX/H-2Db ha lotype [13]. However, since the reciprocal recombinant Hh-1 M-2D" has not been identified, homozygosity for H-2Db may be a necessary but not sufficient condition for the expression of Hh-lb phenotye.…”

P1 and cosmid clones define the organization of 280 kb of the mouse H-2 complex containing the Cps-1 and Hsp70 loci

“…This region is of particular interest because the genes controlling several phenotypic traits appear to map within it. A gene that affects the antibody response to TNP-Ficoll (Shapiro et al 1985), the locus that controls the hematopoietic histocompatibility antigen, Hh-1 (Daley et al 1987), a gene that affects susceptibility to cortisone-induced cleft palate, Cps-1 (Gasser et al 1988), and a gene that affects susceptibility to experimental autoimmune orchitis, Orch-1 (Teuscher et al 1990;Snoek et al 1993), have all been localized to this interval. The isolation of this portion of the mouse H-2 complex in molecular clones will facilitate the identification of these functionally defined genes.…”

Homopoietic histocompatibility (Hh-1) phenotype and the regulation of its expression

“…Control of the specificity is primarily exerted by the Hemopoietic histocompatibility-1 (Hh-1) locus, although other Hh loci are critical in specific haplotypes and strain combinations (Cudkowicz and Nakamura 1983;Cudkowicz and Warner 1979). The Hh-1 locus is closely linked to the H-2D region, and has been mapped to the H-2S/H-2D interval through analysis of intra-H-2 recombinants (Daley et al 1987;Rembecki et al 1987a). Analysis of mutant H-2 haplotypes and variant cell clones indicates that the H-2D class I gene products are not relevant for the expression or recognition of the Hh-1 locuscontrolled structures (Daley et al 1987;Milisauskas et al 1987;Milisauskas and Nakamura 1988).…”