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To investigate the role of an anchoring pocket in allele-specific peptide presentation by a major histocompatibility complex class I molecule, we "transplanted" a B pocket from HLA-A*0201 into HLA-B*2705 by site-directed mutagenesis. The resulting protein, designated B27.A2B, binds a different set of endogenous peptides than B*2705 as evidenced by complete loss of allorecognition as well as restored expression in the antigen processing-defective mutant cell line T2. B27.A2B also fails to present an HLA-B27-restricted influenza virus peptide [nucleoprotein (383-391)] to cytotoxic T lymphocytes (CTLs). However, substitution of leucine, the predominant P2 anchor residue in A*0201-restricted peptides, for arginine, the P2 anchor in nucleoprotein-(383-391) and other B*2705-restricted peptides, restores recognition of B27.A2B by the same B*2705-restricted peptide-specific CTLs. These results demonstrate that a dominant polymorphic pocket in a class I molecule, through interaction with the anchor residue of an antigenic peptide, can distinguish among peptides differing by only a single amino acid and thus determine the allelic specificity of peptide presentation.

Original publication




Journal article


Proceedings of the National Academy of Sciences of the United States of America

Publication Date





6879 - 6883


Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599.


Antigen-Presenting Cells, T-Lymphocytes, Cytotoxic, Cell Line, Arginine, Lysine, Peptide Fragments, RNA-Binding Proteins, Nucleoproteins, Viral Core Proteins, HLA-B27 Antigen, Epitopes, Genes, MHC Class I, Amino Acid Sequence, Structure-Activity Relationship, Mutation, Alleles, Molecular Sequence Data