Sex-dependent effects of non-H-2 loci on lethal GVH reaction induced across an H-2 barrier.
We have studied the influence of DBA/2 non-H-2 antigens on the lethal graft-versus-host reaction (GVHR) developed across an H-2 barrier. (DBA/2 X B10.D2)F1 X B10.D2 (H-2d) backcross (BC) mice were typed for their allelic constitution at nine genetically independent chromosome markers and used as individual cell donors simultaneously for two to three (DBA/2 X B10.D2)F1 recipients incompatible for DBA/2 non-H-2 antigens alone and two to three (DBA/2 X B10.BR)F1 recipients incompatible for DBA/2 non-H-2 antigens and H-2k. The results showed that, when compared with that developed in a control group incompatible for H-2k alone [B10.D2----(B10.D2 X B10.BR)F1]; the GVHR mortality seen in the presence of an additional incompatibility for DBA/2 non-H-2 antigens [(DBA/2 X B10.BR)F1 recipients] is significantly delayed but only in female mice. An analysis of individual BC donors indicated that this protective effect of DBA/2 non-H-2 antigens correlates with incompatibility for gene(s) linked to the Pgm-1 chromosome marker. In contrast, incompatibility for gene(s) linked to Mod-1 and Es-3 markers accelerates GVHR mortality, but only in male mice. Finally, the results obtained with (DBA/2 X B10.D2)F1 and (DBA/2 X B10.BR)F1 recipients were compared; they showed that the intensity of the GVHR developed by cells from individual BC donors against a given set of DBA/2 non-H-2 antigens correlates well with that developed by the same BC donor against the same set of non-H-2 antigens plus H-2k. We conclude that certain non-H-2 genes (and antigens) can modulate the intensity of the GVHR developed across an H-2 barrier. The number of such genes is probably great; their effects are strong and complex, and can be sex-dependent.
D000818:Animals; D002874:Chromosome Mapping; D005260:Female; D008040:Genetic Linkage; D006087:Graft vs Host Reaction; D006183:H-2 Antigens / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA / Q000276:immunology; D012737:Sex Factors
D006183:H-2 Antigens; D006649:Histocompatibility Antigens