Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide.

Journal article

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.

Authors: Colbert, R; Rowland-Jones, S; Mcmichael, A; Frelinger, J

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 90
• Issue: 14
• Pages: 6879-6883
• Publication date: 1993-07-01
• DOI: 10.1073/pnas.90.14.6879
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Structure-Activity Relationship; Cell Line; Antigen-Presenting Cells; T-Lymphocytes, Cytotoxic; Viral Core Proteins; Lysine; Alleles; RNA-Binding Proteins; Nucleoproteins; Molecular Sequence Data; Peptide Fragments; Genes, MHC Class I; Mutation; Amino Acid Sequence; Epitopes; HLA-B27 Antigen; Arginine