Identification of classical minor histocompatibility antigen as cell-derived peptide

Abstract

Histocompatibility antigens expressed on tissue grafted between individuals are recognized by host T cells, which reject the graft. The major histocompatibility complex (MHC) antigens have been identified on the molecular level, whereas the molecules representing the remaining ones, the minor histocompatibility antigens, are unknown, apart from some exceptions. The cytotoxic T lymphocyte (CTL) response against minor histocompatibility antigens shares many aspects with that against virus-infected cells. Virus-specific CTL recognize peptides derived from viral proteins produced in the infected cell. These peptides are presented by MHC class I molecules, as indicated by functional and crystallographic data. By analogy, minor histocompatibility antigens have been postulated to be peptides derived from normal cellular proteins presented by MHC class I molecules. Here we report that peptides derived from normal cellular proteins can indeed be recognized by CTL raised in the classical minor histoincompatible mouse strain combination, C57BL/6 against BALB.B. Thus, we have proven the above postulate, and isolated one of the minor histocompatibility molecules elusive for several decades.

Assessment of major histocompatibility complex class I interaction with Epstein‐Barr virus and human immunodeficiency virus peptides by elevation of membrane H‐2 and HLA in peptide loading‐deficient cells

“…More than the half of the positive peptides were identified as positives in both assays, but many were positive only in one assay. We have used 24 aa long HIV gag peptides which should be compared with reservation with those of 15 aa long peptides screened in the in vitro assembly assay by Elvin et al In vivo presented "natural" peptides are 8-9 aa long [33,[36][37][38]. The suboptimal 24 aa length of our peptides may explain the observation that none of the HIV-1 gag peptides had as high capacity to enhance class I expression as the shorter control influenza peptides (2-2.9 times and 3.9-5.6 times elevation, respectively; Table 1).…”

The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

“…We show here that this approach, combined with careful attention to the biochemical properties of the naturally processed epitope, resulted in the direct identification of the long sought after immune dominant H2K b -restricted H4 b epitope (1,2,29). Like most other identified autosomally encoded minor H Ags, H4 arises from a single amino acid (P3Thr to isoleucine) change in a conserved, broadly expressed protein (35).…”

“…More than a decade ago, the pioneering work of Rammensee (1,2) and Fischer Lindahl (3,4) and their coworkers independently recognized that minor H Ags are self peptides, derived from proteolytic processing of normal cellular proteins. These self peptides are presented by MHC class I molecules to specific CD8 ϩ T lymphocytes.…”

Identification of an immunodominant mouse minor histocompatibility antigen (MiHA). T cell response to a single dominant MiHA causes graft-versus-host disease.

“…Indeed, class Iand class II-associated self peptides are involved in positive and negative selection of thymocytes, and the former also regulate susceptibility to NK cell-mediated lysis (3)(4)(5)(6). Some of these self peptides, called minor histocompatibility antigens (MiHAs) 1 , are polymorphic and can therefore trigger potent T cell responses between MHC-identical individuals (7). The most important immune reactions elicited by in vivo alloreactivity to MiHA are graft rejection, graft-versus-host disease (GVHD), and graft-versus-tumor effect (8).…”