The functional basis of minor histocompatibility loci.
This work addresses the functional basis of classical minor histocompatibility (H) loci. We focus on the H-3 locus, which is actually a complex genetic unit to which the phenotypic trait of tissue rejection, genes whose products stimulate specific subsets of T cells, and Ir genes have been mapped. To clarify how these genes relate to one another and to the trait of tissue rejection, strains of intra-H-3 recombinant mice were produced and analyzed. These mice allowed us to selectively elicit immune responses to Ag (referred to as type I Ag) that stimulate MHC class I-restricted CTL, or Ag (referred to as type II Ag) that stimulate MHC class II-restricted Th. The splitting of H-3 in this manner resulted in a dramatic diminution of the skin allograft response, and with rare exception, an elimination of the CTL response after spleen cell immunization. A selective response to type I Ag resulted in slow, incomplete skin allograft rejection that demonstrated both CD4+ cell-dependent and -independent components. A selective response to the type II Ag failed to result in allograft rejection. The type II Ag did, however, act as an Ir gene that determined whether responses to type I Ag could occur. Altogether, the results indicate that the trait of tissue rejection associated with H-3 is a consequence of the strongly synergistic effects of Th-CTL collaboration induced by products of type I and type II genes. Moreover, the results suggest a genetic explanation for some of the Ir gene effects associated with H-3.
Roopenian
D C
DC
Jackson Laboratory, Bar Harbor, ME 04609.
Davis
A P
AP
Christianson
G J
GJ
Mobraaten
L E
LE
D000818:Animals; D002460:Cell Line; D005260:Female; D005802:Genes, MHC Class II; D006084:Graft Rejection; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000502:physiology; D008912:Minor Histocompatibility Loci; D011995:Recombination, Genetic; D016038:Skin Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D014184:Transplantation, Homologous
D015778:Minor Histocompatibility Antigens