Allele-Specific B Pocket Transplant in Class I Major Histocompatibility Complex Protein Changes Requirement for Anchor Residue at P2 of Peptide

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 diffe...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1993-07, Vol.90 (14), p.6879-6883
Main Authors: Colbert, Robert A., Rowland-Jones, Sarah L., McMichael, Andrew J., Frelinger, Jeffrey A.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Sequence
Amino acids
Antigen-Presenting Cells - immunology
Antigens
Arginine - immunology
Biological and medical sciences
Cell Line
Cell lines
Epitopes - immunology
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genes, MHC Class I - genetics
Genes, MHC Class I - immunology
Geometric lines
Histocompatibility antigens (hla, h-2 and other systems)
HLA-B27 Antigen - genetics
HLA-B27 Antigen - immunology
Hydrogen bonds
Influenza A virus
Lysine - immunology
Molecular immunology
Molecular interactions
Molecular Sequence Data
Molecules
Mutation
Nucleoproteins - immunology
Peptide Fragments - immunology
RNA-Binding Proteins
Structure-Activity Relationship
T cell antigen receptors
T lymphocytes
T-Lymphocytes, Cytotoxic - immunology
Viral Core Proteins - immunology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.90.14.6879