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J Virol. 2009 Sep;83(18):9206-14. doi: 10.1128/JVI.00932-09. Epub 2009 Jun 24.

T-cell tolerance for variability in an HLA class I-presented influenza A virus epitope.

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1
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, 73104, USA.

Abstract

To escape immune recognition, viruses acquire amino acid substitutions in class I human leukocyte antigen (HLA)-presented cytotoxic T-lymphocyte (CTL) epitopes. Such viral escape mutations may (i) prevent peptide processing, (ii) diminish class I HLA binding, or (iii) alter T-cell recognition. Because residues 418 to 426 of the hypervariable influenza A virus nucleoprotein (NP(418-426)) epitope are consistently bound by class I HLA and presented to CTL, we assessed the impact that intraepitope sequence variability has upon T-cell recognition. CTL elicited by intranasal influenza virus infection were tested for their cross-recognition of 20 natural NP(418-426) epitope variants. Six of the variant epitopes, of both H1N1 and H3N2 origin, were cross-recognized by CTL while the remaining NP(418-426) epitope variants escaped targeting. A pattern emerged whereby variability at position 5 (P5) within the epitope reduced T-cell recognition, changes at P4 or P6 enabled CTL escape, and a mutation at P8 enhanced T-cell recognition. These data demonstrate that substitutions at P4 and/or P6 facilitate influenza virus escape from T-cell recognition and provide a model for the number, nature, and location of viral mutations that influence T-cell cross-recognition.

PMID:
19553306
PMCID:
PMC2738244
DOI:
10.1128/JVI.00932-09
[Indexed for MEDLINE]
Free PMC Article
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