The Journal of Immunology, Vol 151, Issue 9 4595-4605, Copyright © 1993 by American Association of Immunologists

ARTICLES

The functional basis of minor histocompatibility loci

DC Roopenian, AP Davis, GJ Christianson and LE Mobraaten
Jackson Laboratory, Bar Harbor, ME 04609.

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.

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