Detection of two allotype-(Ig-1)-linked minor histocompatibility loci by the use ofH-2-restricted cytotoxic lymphocytes in congenic mice.

Cytotoxic lymphocytes (CTL) were generated betweenIg-1-congenic strains BALB/c(H-2(d),Ig-1(a)) andC.B-17(H-2(d),Ig-1(b)) by cross-immunization in both directions and rechallenge in vitro. The effector cell populations specifically lysed target cells sharing both theH-2 haplotype and theIg-1 allele of the sensitizing strain. B- and T-cell blasts were equally good targets, suggesting thatH-2-restricted cytotoxic lymphocytes are not directed against serologically defined conventional allotypic determinants, but probably against minor histocompatibility antigens controlled by genes linked to theIg-1 complex. Competition experiments using cold target cells from a series ofIg-1(b)-congenic strains of the BALB/c background (BAB-14, C.B-17, C.B-26) revealed two not yet described minor histocompatibility loci linked to theIg-1 complex: We could demonstrate that BALB/c anti-C.B-17 effector cells recognize at least two distinct antigenic determinants on C.B-17 target cells, but only one on target cells from BAB-14, which carries a recombinantIg-1 complex. From these results we conclude that one of the minor histocompatibility antigens, designated as H(C(H)), is encoded by a gene linked to the heavy-chain constant-region (C(H)) genes, whereas the second minor histocompatibility antigen, designated as H(V(H)), is coded for by a gene linked to the heavy-chain variable-region (V(H)) genes. These two new genetic markers may be useful for further analysis of the mouseIg-1 complex because the analysis of the H(C(H)) and H(V(H)) genes may facilitate the search for recombinants in that chromosomal region.