Giuseppe
Emeritus
J Virol. 2009 Jun 24. [Epub ahead of print]
T Cell Tolerance for Variability in a Class I HLA Presented Influenza A Virus Epitope.
Wahl A, McCoy W, Schafer F, Bardet W, Buchli R, Fremont DH, Hildebrand WH. Department of Microbiology and Immunology, 975 NE 10 Street, Oklahoma City, Oklahoma, 73104 USA; Department of Pathology and Immunology, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110 USA; and Pure Protein L.L.C., 800 Research Parkway, Suite 340, Oklahoma City, OK 73104 USA.
To escape immune recognition, viruses acquire amino acid substitutions in class I Human Leukocyte Antigen (HLA) presented CTL epitopes. Such viral escape mutations may (i) prevent peptide processing, (ii) diminish class I HLA binding, or (iii) alter T cell recognition. Because the hypervariable influenza A virus nucleoprotein (NP)418-426 epitope is consistently bound by class I HLA and presented to cytotoxic T-lymphocytes (CTL), we assessed the impact that intra-epitope sequence variability has upon T cell recognition. CTL elicited by intranasal influenza infection were tested for their cross-recognition of 20 natural NP418-426 epitope variants. Six of the variant epitopes, of both H1N1 and H3N2 origin, were cross-recognized by CTL while the remaining NP418-426 epitope variants escaped targeting. A pattern emerged whereby variability at P5 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 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 [PubMed - as supplied by publisher]
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T Cell Tolerance for Variability in a Class I HLA Presented Influenza A Virus Epitope.
Wahl A, McCoy W, Schafer F, Bardet W, Buchli R, Fremont DH, Hildebrand WH. Department of Microbiology and Immunology, 975 NE 10 Street, Oklahoma City, Oklahoma, 73104 USA; Department of Pathology and Immunology, Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110 USA; and Pure Protein L.L.C., 800 Research Parkway, Suite 340, Oklahoma City, OK 73104 USA.
To escape immune recognition, viruses acquire amino acid substitutions in class I Human Leukocyte Antigen (HLA) presented CTL epitopes. Such viral escape mutations may (i) prevent peptide processing, (ii) diminish class I HLA binding, or (iii) alter T cell recognition. Because the hypervariable influenza A virus nucleoprotein (NP)418-426 epitope is consistently bound by class I HLA and presented to cytotoxic T-lymphocytes (CTL), we assessed the impact that intra-epitope sequence variability has upon T cell recognition. CTL elicited by intranasal influenza infection were tested for their cross-recognition of 20 natural NP418-426 epitope variants. Six of the variant epitopes, of both H1N1 and H3N2 origin, were cross-recognized by CTL while the remaining NP418-426 epitope variants escaped targeting. A pattern emerged whereby variability at P5 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 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 [PubMed - as supplied by publisher]
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