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

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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
StatePublished - 1995

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T-Lymphocyte Epitopes
Cytotoxic T-Lymphocytes
Human Influenza
Transgenic Mice
Epitopes
Proteins
Peptides
Immunodominant Epitopes
Forensic Anthropology
Vaccinia virus
Amino Acid Sequence
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Immunology

Cite this

Man, S., Newberg, M. H., Crotzer, V. L., Luckey, J., Williams, N. S., Chen, Y., ... Engelhard, V. H. (1995). Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice. International Immunology, 7(4), 597-605.

Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice. / Man, S.; Newberg, M. H.; Crotzer, V. L.; Luckey, J.; Williams, N. S.; Chen, Y.; Huczko, E. L.; Ridge, J. P.; Engelhard, V. H.

In: International Immunology, Vol. 7, No. 4, 1995, p. 597-605.

Research output: Contribution to journalArticle

Man, S, Newberg, MH, Crotzer, VL, Luckey, J, Williams, NS, Chen, Y, Huczko, EL, Ridge, JP & Engelhard, VH 1995, 'Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice', International Immunology, vol. 7, no. 4, pp. 597-605.
Man, S. ; Newberg, M. H. ; Crotzer, V. L. ; Luckey, J. ; Williams, N. S. ; Chen, Y. ; Huczko, E. L. ; Ridge, J. P. ; Engelhard, V. H. / Definition of a human T cell epitope from influenza A non-structural protein 1 using HLA-A2.1 transgenic mice. In: International Immunology. 1995 ; Vol. 7, No. 4. pp. 597-605.
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AU - Newberg, M. H.

AU - Crotzer, V. L.

AU - Luckey, J.

AU - Williams, N. S.

AU - Chen, Y.

AU - Huczko, E. L.

AU - Ridge, J. P.

AU - Engelhard, V. H.

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AB - 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.

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