Physical association between MHC class I molecules and immunogenic peptides

Abstract

ANTIGENIC peptides are presented to T lymphocytes by major histocompatibility complex (MHC) molecules^1–14. The binding of peptides to MHC class II molecules has been demonstrated directly, and is found to correlate with the ability of specific class II alleles to restrict the T-cell response to specific peptides^2–8. By comparison, a direct demonstration of a physical association between antigenic peptides and MHC class I molecules has proved difficult. A recent report¹⁵ shows that it is possible, however, and the three-dimensional structure of a class I MHC molecule^16,17illustrates the site where such binding must occur. Here we describe a simple assay which measures the binding of radiolabelled MHC class I molecules to peptides bound to a solid phase support. We find that class I molecules bind specifically to peptides known to be antigenic for class I-restricted cytotoxic T lymphocytes. Peptides which are recognized by cytotoxic T lymphocytes bind not only to the restricting MHC class I molecule but also to other class I molecules. Our results suggest that quantitative differences in the peptide/MHC class I interaction may influence the pattern of MHC restriction observed in vivo.