Mapping the orientation of an antigenic peptide bound in the antigen binding groove of H-2Kb using a monoclonal antibody.

Joyce S, Sun R, Nathenson SG
Biochem Biophys Res Commun. 1992 186 (3): 1449-54

PMID: 1380802 · DOI:10.1016/s0006-291x(05)81569-4

The major histocompatibility complex class I molecules are receptors for intracellular peptides, both of self and non-self origin. When non-self peptides (eg., pathogen derived) are bound to the class I molecules, they form ligands for T cell receptors resulting in antigen specific lysis of the infected cells by cytotoxic T lymphocytes. Therefore, an understanding of the process of antigen recognition requires the precise definition of the structural features of the bimolecular complex formed by a single well defined antigenic peptide bound to the class I molecule. A strategy using antibodies was developed to probe the structural features of the H-2Kb containing a defined peptide in the antigen cleft. We report that the binding surface area of a Kb specific monoclonal antibody (28-13-3s) includes residues in the alpha 1 (Gly56 and Glu58) and alpha 2 (Trp167) helices of Kb thus, binding across the antigen binding groove. When cells treated with the antigenic peptide of vesicular stomatitis virus, N52-59, and its alanine substituted analogs were tested for 28-13-3s binding, it was found that position 1 of the peptide also forms a part of the antibody binding site. This finding strongly supports the positioning of the N-terminus of N52-59 proximal to pocket A, thus, assuming an orientation parallel to the alpha 1 helix.

MeSH Terms (16)

Abelson murine leukemia virus Amino Acid Sequence Animals Antibodies, Monoclonal B-Lymphocytes Cell Line Epitopes Genes, MHC Class I H-2 Antigens Mice Models, Molecular Molecular Sequence Data Polymerase Chain Reaction Protein Conformation Rauscher Virus T-Lymphocytes

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