The first recognition of MHC genes was based on their ability to encode proteins that serve as identity markers on tissues and cells that have been transplanted into an incompatible recipient. Their recognition by the recipient’s lymphocytes leads to prompt rejection. The preoccupation of investigators with the role of histocompatibility antigens in transplantation obscured their real purpose of serving as identity markers on cells interacting with T cells carrying out specific immune functions through their own T cell receptors. In fact, T lymphocytes recognize antigens only in the context of MHC molecules.