[Current concepts on the alloreactive response]

Many new data have been obtained in the last 4 years about the structure and the functions of Major Histocompatibility Complex (MHC) molecules. Structural data are summarized and the functions of MHC molecules in the presentation of peptides to T cells is described. The high selectivity of peptides binding to MHC molecules is explained. The negative and positive selection of T cells in the thymus is described and the notion of repertoire introduced. The consequences of these new data on the understanding of H2 restriction and alloreactivity are explained. The 4 potential types of alloreactivity are defined: 1) House keeping gene (HKG) peptides bound to allogenic MHC molecules, 2) allogenic peptides (derived from allogenic MHC molecules) bound to allogenic MHC molecules, 3) empty allogenic MHC molecules, 4) allogenic peptides bound to autologous MHC molecules. In fact, the allogenic response is mostly directed toward HKG peptides bound to the allogenic MHC molecules of the graft cells (type 1). The potential role of type 4 alloreactivity in rejection is discussed.