Evidence for a histocompatibility locus probably linked to but distinct from Mls and H-25.

BALB/c (Mlsb) and BALB.D2-Mlsa strains of mice, both H-2d, are congenic and differ for the Mls locus (and linked genes) located on chromosome 1. The BALB.D2-Mlsa strain was obtained by introducing the Mlsa allele of DBA/2 mice into BALB/c mice. In previous studies we showed that BALB.D2-Mlsa recipients reject, relatively rapidly, all skin grafts from BALB/c donors. We and other groups have questioned whether the rejections observed were indeed due to the incompatibility for Mlsb products or for products of a histocompatibility (non-H-2) locus linked to, but distinct from, Mlsb. To answer this question, several hybrids carrying either Mlsa or Mlsb in various genetic contexts were grafted with skin from Mls-compatible BALB/c or BALB.D2-Mlsa donors; in the genetic combinations selected, any rejection which might occur would reflect the effects of a non-Mls incompatibility between BALB/c and BALB.D2-Mlsa strains. In certain of the donor-recipient combinations studied, the skin grafts were tolerated for greater than 200 days, but a relatively rapid rejection of BALB/c skin grafts was observed in (B10.D2 x BALB.D2-Mlsa)F1 and (B10.BR x BALB. D2-Mlsa)F1 hybrid recipients. These results indicated that in addition to Mls, the BALB/c and BALB.D2-Mlsa strains differ for at least one other non-H-2 histocompatibility locus. The possible involvement of H-25 was then investigated. Indeed, disparity for H-25, which maps on chromosome 1 close to Mls, can induce relatively rapid skin graft rejection. The H-25 allele of the DBA/2 strain has not been defined: we considered, therefore, that BALB/c and DBA/2 could be disparate at the H-25 locus, and that H-25 (transmitted by DBA/2 to the BALB.D2-Mlsa strain, together with the Mlsa allele) could be responsible for the skin graft rejection we observed. Our results showed, however, that DBA/2, BALB/c and BALB.D2-Mlsa strains of mice all share the H-25c allele; they therefore ruled out a role for H-25 incompatibility in the skin graft rejections we observed, and indicated that these rejections are due to the effects of a yet undefined histocompatibility locus (locus 'x'), probably linked to, but distinct from, the Mls locus. Further experiments showed that the histocompatibility effect of locus 'x' cumulates with that exhibited by Mlsb (or by a putative histocompatibility locus linked to Mlsb).