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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


Proc Natl Acad Sci U S A

Publication Date





6879 - 6883


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