In this article, Derry Roopenian relates the tradition, ll view of nlinor histocompatibility (H) loci to recent advances in understanding of the tissue rejection process and the molecular nature of minor histocompatibility antigens. He proposes that minor H loci can be subdivided by the ability of their products to stimulate different T-cell subsets and discusses the implications of this concept m terms of the origins and behavior of minor H loci and their antigens, tumor immunology and autoimmunity.

H loci were first identified in tumor transplantation studies at the beginning of the twentieth century. These classic studies demonstrated that tumors could be transplanted among mice of the same'race'but failed to survive in mice of different races (reviewed m Ref. 1). Little and Tyzzer 2 showed a genetic basis for rejection or acceptance of tumor grafts and estimated that (a minimum of) 14-15 independently-segregating loci were responsible. After it had become apparent that these loci determined acceptance and rejection, not only of neoplastic tissue but also of normal tissue, Snell 4 named them histocompatibility (H) loci. One of these loci, H-2, was the mouse major histocompatibility complex (MHC). The remaining H loci were characterized by weaker immunological rejection compared with that elicited by H-2 and were, therefore, named minor H loci. This article focusses on the genetic organization of minor H loci and its implications; for excellent, more comprehensive, reviews, the reader is referred to Perreault et al. 5 and Loveland and Fischer Lindahl". Historically, minor H loci have been viewed as independently-segregating genetic units that are monitored by the trait of tissue rejection. More than 40 minor H loci, identified primarily by such methods, have been positioned on the mouse chromosomal map 7. Nevertheless, minor H loci remain poorly understood because tissue rejection is the endpoint of a complex series of events including minor H gene expression, processing and presentation of the products on MHC proteins, interaction among the T-cell subsets and eventual tissue destruction. Elucidation of many of these events is necessary to understand the loci and the antigens they encode.