Homozygosity at the major histocompatibility complex is required for optimal immunogenicity of bone marrow cell allografts in irradiated rats.

Hemopoietic histocompatibility (Hh) Genes associated with the H-2 region control the antigenicity of hemopoietic cell grafts in the mouse. We have tested for similar genes in rats. Wistar Furth (WF, RTlu) or Lewis (LEW RTl1) bone marrow cell grafts did not proliferate in spleens of lethally irradiated (WFxLEW) F1 hybrid rats as assessed by measuring the incorporation of 5-iodo-2' deoxyuridine - 125I (IUdR) into recipient spleens 5 days after transplantation. In contrast, (WFxLEW) F1 hybrid marrow cells grew well in both WF and LEW parental strain hosts. (WFxLEW) F1 or (WFxLEW) F1 hybrid rats were backcrossed to WF parental strain rats to produce progeny, either homozygous, or heterozygous for the MHC. The RTl type of 46 individual backcross progeny was determined using a 5 day mixed-lymphocyte reaction (MLR). Correlation between RTl type and growth of marrow grafts of individual backcross rats were determined by using each rat as a bone marrow donor for irradiated LEW hosts. Marrow grafts from rats heterozygous for RTl were accepted in all 25 cases, whereas, grafts from 19 to 21 homozygous donors were rejected by the LEW hosts. Thus, homozygosity, for Hh determinants in or near the RTl region appears to be necessary for optimal immunogenicity of bone marrow allografts.