Structural Intermediates in the Reactions of Antigenic Peptides with MHC Molecules

Molecular complexes of class I and class II major histocompatibility complex (MHC) molecules and antigenic peptides are recognized by specific cytotoxic and helper lymphocytes (Schwartz 1985; Townsend and Bodmer 1989). Class II MHC/peptide complexes reconstituted in planar lipid bilayers are recognized by specific T-helper cells (Watts et al. 1984,1985). That is, specific antigenic peptides bind to affinity-purified class II MHC molecules in lipid membranes, the resulting MHC/peptide complexes have long lifetimes (Watts and McConnell 1986), and even after extensive washing, such MHC/peptide complexes trigger specific T-helper cells to release interleukin-2. However, there are major questions as to the mechanism by which exogenous peptides bind to MHC molecules in bilayer membranes. Such questions are raised by the difficulty of preparing MHC/peptide complexes of defined stoichiometry, with many preparations only showing 5–10% binding of added peptide (Watts and McConnell 1986; Sadegh-Nasseri and McConnell 1989). This raises the issue of the possible role...