Transplantation Immunology: Peptides in the groove cause histocompatibility

Abstract

Organ and bone marrow transplantation is frequently complicated by immune responses against major and minor histocompatibility antigens. This article will discuss current concepts of the molecular nature of histocompatibility antigens. The functional units that trigger immune responses by T lymphocytes are peptides bound to the peptide binding groove of major histocompatibility complex (MHC) class I and class II molecules. In MHC mismatched transplant situations, T lymphocytes recognise donor MHC molecules displaying donor derived peptides. In MHC matched transplant situations, T cell immunity is directed against donor-specific peptides bound to the groove of MHC molecules. These donor-specific peptides are derived from polymorphic cellular proteins, named minor histocompatibility (mH) antigens. We propose that immune responses against mismatched MHC antigens and mH antigens are probably directed against a small number of immunodominant peptides. In future, it may become possible to exploit such peptides for tolerance induction, which may lead to specific downregulation of unwanted T cell responses in organ and bone marrow transplantation.