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

Robert A. Colbert, Sarah L. Rowland-Jones, Andrew J. Mcmichael, Jeffrey A Frelinger

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)6879-6883
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number14
StatePublished - Jul 15 1993
Externally publishedYes

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Major Histocompatibility Complex
Alleles
Transplants
Peptides
Proteins
Nucleoproteins
Cytotoxic T-Lymphocytes
HLA-B27 Antigen
Antigen Presentation
Site-Directed Mutagenesis
P2 peptide
Orthomyxoviridae
Leucine
Arginine
Amino Acids
Cell Line

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Allele-specific B pocket transplant in class I major histocompatibility complex protein changes requirement for anchor residue at P2 of peptide. / Colbert, Robert A.; Rowland-Jones, Sarah L.; Mcmichael, Andrew J.; Frelinger, Jeffrey A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 90, No. 14, 15.07.1993, p. 6879-6883.

Research output: Contribution to journalArticle

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