SOLUTION BINDING OF AN ANTIGENIC PEPTIDE TO A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULE AND THE ROLE OF BETA-2-MICROGLOBULIN

The major histocompatibility complex-encoded class I molecule, a noncovalent dimer of a polymorphic 45-kDa heavy chain and a nonpolymorphic 12-kDa beta-2-microglobulin (beta-2m) light chain, binds peptide antigen prior to its interaction with T-cell antigen receptors. We report here that the binding in aqueous solution at 37-degrees-C of a soluble purified murine major histocompatibility complex class I protein, H-2L(s)d (a soluble analogue of H-2L(d) consisting of the alpha-1 and alpha-2 domains of H-2L(d), the alpha-3 domain and the C terminus of Q10b), to an antigenic peptide is controlled by the light-chain subunit beta-2m. Analysis of the equilibrium binding data favors a model in which two classes of peptide binding sites exist, the high-affinity class having an equilibrium constant for dissociation, K(H), of 3.7 x 10(-7) M and accounting for 12% of the theoretically available sites. Studies of binding in the presence of excess beta-2m indicate that this increases the concentration of available high-affinity sites. These data are consistent with a ternary model in which high-affinity sites are generated by the interaction Of beta-2m With the peptide-binding class I heavy chain.