Bone marrow cell transplants involving donors and hosts with haplotypes derived from spretus mice

Intra-H2 recombinant inbred mice derived from matings between BIO (H2^b) and B10.SP2 (H2^sp2) mice, with an H2 haplotype derived from Mus spretus, have been used to map genes at H2. Recombinants 10115, 10484, R40,9347, and 9950 were used as donors or hosts in bone marrow cell (BMC) transplants in irradiated mice. From previous studies of Mus musculus mice, the antigens (Ag) on BMC appear to be inherited re- cessively. The mechanisms offered include codominant inheritance of transacting genes that regulate expression of BMC Ag (Hh hypothesis) and codominant inheritance of class I Ag motifs capable of sending “negative signals” to effector natural killer (NK) cells (missing self hypothesis). Our results indicate that stem cell donors that express the same class I Ag, but differ at genes between Bat2 and Tnfa in the H2- S/D interval, can differ in immunogenicity of transplanted stem cells. The structural gene for the H2^sp2Ag appears to map telomeric of Bat2 and is codominantly inherited. An H2^bgene capable of inhibiting expression of the H2^sp2Ag (or contributing to class I motifs capable of inhibiting NK cell mediated lysis of H2^sp2BMC) maps in the Bat2/Tnfa gene segment, but requires homozygosity for this function and may require the H2-D^bgene as well. Although H2^sp2hosts reject H2^bBMC, hosts (10115, 10484, R40, and 9347 strain) that are H2^bin the centromeric, and H2^sp2in the telomeric, portion of H2 accept H2^bBMC grafts. These two observations have not been made with haplotypes entirely of Mus musculus origin. The data do not support the Hh hypothesis, and are consistent with the missing self hypothesis only if the gene (requiring homozygozity for function) in the Bat2/Tnfa region codes for a particular protein or peptide that associates with D^bto generate a “protective motif.”