Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice

S. Man, M. H. Newberg, V. L. Crotzer, J. Luckey, N. S. Williams, Y. Chen, E. L. Huczko, J. P. Ridge, V. H. Engelhard

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Previous results from this laboratory demonstrated that the dominant influenza A epitope recognized by HLA-A2.1-restricted cytotoxic T lymphocytes (CTL) from HLA-A2.1 transgenic mice was the matrix protein 1 (M1) peptide epitope that is immunodominant in human CTL responses. However, analysis of a large number of CTL lines revealed a subset of influenza A/PR/8/34-specific murine CTL that recognized an HLA-A2.1-restricted epitope distinct from M1. Using recombinant vaccinia viruses encoding different influenza gene segments, the epitope recognized by these CTL was shown to be derived from A/PR/8 non-structural protein 1 (NS1). Because these CTL did not-recognize targets infected with the A/Alaska/6/77 strain of influenza, candidate peptide epitopes were synthesized based on sequences that included an HLA-A2.1-specific binding motif, and that differed between A/PR/8 and A/Alaska. All of these CTL recognized a nonamer and a decamer peptide which contained a common eight amino acid sequence and two distinct sets of binding motif residues. However, the nonamer peptide was able to sensitize CTL for half-maximal lysis at 80- to 2500-fold lower doses than either the octamer or decamer. The homologous peptide derived from A/Alaska NS1 contained conservative amino acid changes at positions 4 and 8, and was not recognized at any tested concentration, although it bound with higher affinity to HLA-A2.1 than the peptide from A/PR/8. The A/PR/8 NS1 nonamer epitope was also recognized by human influenza A-specific CTL derived from two individuals. These results substantiate the general utility of HLA class I transgenic mice for the identification of human CTL epitopes for other pathogens.

Original languageEnglish (US)
Pages (from-to)597-605
Number of pages9
JournalInternational Immunology
Volume7
Issue number4
DOIs
StatePublished - Jan 1 1995

Keywords

  • HLA-A2.1
  • Influenza
  • Non-structural protein 1
  • T cell epitope

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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