Hemopoietic histocompatibility (Hh-1) regulatory and structural genes of the F haplotype map to H-2

Natural resistance to bone marrow stem cell (BMC) grafts in lethally irradiated mice is a consequence of natural killer cell recognition and elimination of BMC that express hemopoietic histocompatibility (Hh) antigens inherited noncodominantly. The major Hh genetic region, Hh-1, maps to H-2. The phenotype of the BMC was determined by grafting BMC into panels of irradiated mice, and measuring splenic incorporation of the radioactive specific DNA precursor, 5-iodo-2′-deoxyu-ridine [¹²⁵I] (IUdR) 5 days after cell transfer. Our previous analysis of Hh-1 antigen expression on BMC of intra-H-2 recombinant inbred strain mice indicated that Hh-1 regulatory genes (Hh-lr) map in the H-2S/H-2D interval. Nine recombinants described here shared the following: (1) the DL region was donated by H-2′ that was associated with expression of determinant 2, shared with H-2^d/Hh-1^d, and (2) had crossovers in the S/D or E_a/S intervals or within E_b, and (3) had BMC that were Hh-1 null. F₁hybrids of crosses between mice of these recombinant strains with H-2^dstrain mice had BMC that expressed determinant 2, suggesting that a structural gene had been lost by the crossover event. Crosses with H-2^bstrain mice produced mice whose BMC were Hh-1 null, indicating that the H-2′/Hh-1′ regulatory genes were still intact. We suggest that Hh-1r maps to the S/D interval of all haplotypes so far studied, even H-2′. The structural gene for the f haplotype is centromeric of E_band may be K′, based on recent data supporting the role of class I antigens in Hh antigen expression.