PMID- 19553306
OWN - NLM
STAT- MEDLINE
DCOM- 20091002
LR  - 20240229
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 83
IP  - 18
DP  - 2009 Sep
TI  - T-cell tolerance for variability in an HLA class I-presented influenza A virus 
      epitope.
PG  - 9206-14
LID - 10.1128/JVI.00932-09 [doi]
AB  - 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.
FAU - Wahl, Angela
AU  - Wahl A
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Oklahoma City, 73104, USA.
FAU - McCoy, William 4th
AU  - McCoy WH 4th
FAU - Schafer, Fredda
AU  - Schafer F
FAU - Bardet, Wilfried
AU  - Bardet W
FAU - Buchli, Rico
AU  - Buchli R
FAU - Fremont, Daved H
AU  - Fremont DH
FAU - Hildebrand, William H
AU  - Hildebrand WH
LA  - eng
GR  - HHSN266200400027C/AI/NIAID NIH HHS/United States
GR  - T32 AI007633/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090624
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Antigens, Viral)
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (NP protein, Influenza A virus)
RN  - 0 (Nucleocapsid Proteins)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Viral Core Proteins)
SB  - IM
MH  - Antigen Presentation
MH  - Antigens, Viral
MH  - Cross-Priming
MH  - Epitopes/*genetics
MH  - Histocompatibility Antigens Class I/*immunology
MH  - *Immune Tolerance
MH  - Influenza A Virus, H1N1 Subtype
MH  - Influenza A Virus, H3N2 Subtype
MH  - Influenza A virus/*immunology
MH  - *Mutation, Missense
MH  - Nucleocapsid Proteins
MH  - RNA-Binding Proteins/*immunology
MH  - T-Lymphocytes/*immunology
MH  - Viral Core Proteins/*immunology
PMC - PMC2738244
EDAT- 2009/06/26 09:00
MHDA- 2009/10/03 06:00
PMCR- 2010/03/01
CRDT- 2009/06/26 09:00
PHST- 2009/06/26 09:00 [entrez]
PHST- 2009/06/26 09:00 [pubmed]
PHST- 2009/10/03 06:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - JVI.00932-09 [pii]
AID - 0932-09 [pii]
AID - 10.1128/JVI.00932-09 [doi]
PST - ppublish
SO  - J Virol. 2009 Sep;83(18):9206-14. doi: 10.1128/JVI.00932-09. Epub 2009 Jun 24.