Tissue- and Organ-Specific Immune Responses: Role in Human Disease and Allograft Immunity

Abstract

B efore the crystallization of a major histocompatibility complex (MHC) class I molecule’ or the development of the concept that cellular peptides are presented on the cell surface in association with MHC class I2 cell surface differences within an individual were thought to be due primarily to nonMHC antigens. In contrast, any allogeneic response between individuals with disparate human leukocyte antigens (I-IU) was thought to be essentially a response against the mismatched HLA antigens alone, independent of any bound peptide. Indeed, this concept is the rationale for the current clinical cross-match system for organ allografts, which assumes that the donor peripheral blood leukocytes (PBL) used in the serological cross match represent the full complement of cell surface antigens expressed on the cells of the organ allograft. Recently, it has become increasingly clear that the T lymphocyte recognizes epitopes formed by a combination of an MIX molecule with a specific bound peptide expressed on the cell surface of a target cell. The importance of the presence of the bound peptide and its exact amino acid sequence is emphasized by extensive experimental evidence. Absence of the bound peptide or a change in a single conservative amino acid can attenuate or even completely abrogate T cell recognition or response. The peptide associated with an MHC class I molecule is generally derived from the endogenous pool of available proteins, If a cell within a tissue or organ has a unique function relative to other cells located in other tissues or organs, it should, in turn, express proteins uniquely tailored for that specific function. These proteins can potentially be degraded into peptides and presented by a class I molecule to serve as an epitope unique to