The role of peptides in T cell alloreactivity is determined by self-major histocompatibility complex molecules

By analyzing T cell responses against foreign major histocompatibility comp lex (MHC) molecules loaded with peptide libraries and defined self- and vir al peptides, we demonstrate a profound influence of self-MHC molecules on t he repertoire of alloreactive T cells: the closer the foreign MHC molecule is related to the T cell's MHC, the higher is the proportion of peptide-spe cific, alloreactive ("allorestricted") T cells versus T cells recognizing t he foreign MHC molecule without regard to the peptide in the groove. Thus, the peptide repertoire of alloreactive T cells must be influenced by self-M HC molecules during positive or negative thymic selection or peripheral sur vival, much like the repertoire of the self-restricted T cells. In conseque nce, allorestricted, peptide-specific T cells (that are of interest for cli nical applications) are easier to obtain if T cells and target cells expres s related MHC molecules.