CRYSTALLOGRAPHIC ANALYSIS OF ENDOGENOUS PEPTIDES ASSOCIATED WITH HLA-DR1 SUGGESTS A COMMON, POLYPROLINE II-LIKE CONFORMATION FOR BOUND PEPTIDES

The structure of the human major histocompatibility complex (MHC) clas s II molecule HLA-DR1 derived from the human lymphoblastoid cell line LG-2 has been determined in a complex with the Staphylococcus aureus e nterotoxin B superantigen. The HLA-DR1 molecule contains a mixture of endogenous peptides derived from cellular or serum proteins bound in t he antigen-binding site, which copurify with the class II molecule. Co ntinuous electron density for 13 amino acid residues is observed in th e MHC peptide-binding site, suggesting that this is the core length of peptide that forms common interactions with the MHC molecule. Electro n density is also observed for side chains of the endogenous peptides. The electron density corresponding to peptide side chains that intera ct with the DR1-binding site is more clearly defined than the electron density that extends out of the binding site. The regions of the endo genous peptides that interact with DR1 are therefore either more restr icted in conformation or sequence than the peptide side chains or amin o acids that project out of the peptide-binding site. The hydrogen-bon d interactions and conformation of a peptide model built into the elec tron density are similar to other HLA-DR-peptide structures. The bound peptides assume a regular conformation that is similar to a polyproli ne type II helix. The side-chain pockets and conserved asparagine resi dues of the DR1 molecule are well-positioned to interact with peptides in the polyproline type II conformation and may restrict the range of acceptable peptide conformations.