HIGH-AFFINITY REACTIONS BETWEEN ANTIGEN-SPECIFIC T-CELL RECEPTORS AND PEPTIDES ASSOCIATED WITH ALLOGENEIC AND SYNGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I PROTEINS

We report here that the intrinsic affinities of the antigen-specific T-cell receptors (TCR) of two unrelated CD8(+) T-cell clones for their respective peptide-major histocompatibility complex (MHC) ligands are higher than the values generally thought to prevail for TCR. The TCR of one clone (2C) binds an allogeneic class I MHC protein (L(d)) in association with an alpha-ketoglutarate dehydrogenase nonapeptide (QLSPFPFDL, termed QL9) with an intrinsic affinity (intrinsic equilibrium association constant) of 1-2 x 10(7) M(-1). The TCR of the other clone (4G3) binds a syngeneic class I MHC protein (K-b) in association with an ovalbumin octapeptide (SIINFEKL, termed pOV8) with an intrinsic affinity of 1.5 x 10(6) M(-1). A comparison of the two clones, combined with current views of T-cell repertoire selection in the thymus, leads us to propose that TCR affinities are generally likely to be higher for allogeneic MHC-peptide complexes than for syngeneic MHC-peptide complexes.