ALLOANTIBODIES CAN DISCRIMINATE CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES ASSOCIATED WITH VARIOUS ENDOGENOUS PEPTIDES

Molecules encoded by a single major histocompatibility complex class I gene can associate with any one of a large number of peptide ligands. T-cell receptors have the capacity to discriminate among these peptid e-class I complexes and in many cases bind only a single peptide-class I complex with sufficient affinity to trigger effector function. In c ontrast, it is generally assumed that class I-specific alloantibodies are indifferent to peptide heterogeneity, being directed toward allele -specific determinants on the molecule. In this report, three monoclon al antibodies were used to precipitate K(b) molecules from cell lysate s. Surprisingly, in each case a different set of peptides was found to be associated with K(b) as detected by peptide-dependent K(b)-specifi c alloreactive cytolytic T lymphocytes or by biochemical resolution. T hese results demonstrate that the affinity of binding by alloantibodie s can be affected by the endogenous peptide ligand.