Crystal structure of MHC class II I-Ab in complex with a human CLIP peptide:: Prediction of an I-Ab peptide-binding motif

Association between the class 11 major histocompatibility complex (MHC) and the class 11 invariant chain-associated peptide (CLIP) occurs naturally as an intermediate step in the MHC class 11 processing pathway. Here, we report the crystal structure of the murine class 11 MHC molecule I-A(b) in complex with human CLIP at 2.15 Angstrom resolution. The structure of I-A(b) accounts, via the peptide-binding groove's unique physicochemistry, for the distinct peptide repertoire bound by this allele. CLIP adopts a similar conformation to peptides bound by other I-A alleles, reinforcing the notion that CLIP is presented as a conventional peptide antigen. When compared to the related HLA-DR3/CLIP complex structure, the CLIP peptide displays a slightly different conformation and distinct interaction pattern with residues in I-A(b). In addition, after examining the published sequences of peptides presented by I-A(b), we discuss the possibility of predicting peptide alignment in the I-A(b) binding groove using a simple scoring matrix. (C) 2003 Elsevier Science Ltd. All rights reserved.