title: Longitudinal analysis of an HLA-B*51-restricted epitope in integrase reveals immune escape in early HIV-1 infection.
abstract: OBJECTIVE
  To fully define cytotoxic T-lymphocyte (CTL) escape variants of an HLA-B*51-restricted integrase epitope in early HIV-1 infection.
  
  
  METHODS
  Ninety-four longitudinally sampled acute/early HIV-1 subtype B-infected participants were assessed to determine HLA-B*51-restricted LPPVVAKEI (LI9) escape variants.
  
  
  METHODS
  LI9 was sequenced at baseline and subsequent time points. Interferon-γ (IFNγ) ELISpot assays were performed using serial log dilutions of variant LI9 peptides to determine the cellular response and functional avidity.
  
  
  RESULTS
  There is a significant association between HLA-B*51 expression and an evolving LI9 sequence from baseline to year 1 (P < 0.0001). We detected that the V32I and P30X polymorphisms emerged within HLA-B*51 participants over time. Reversion of the P30S polymorphism was observed by year 1 in one HLA-B*51 participant. LPPIIAKEI and LPSIVAKEI had significantly lower functional avidity compared with LPPVVAKEI and so may be less well recognized by LI9-specific CTLs; a positive IFNγ response to IPSVVAKEI was rarely seen. Functional avidity to wild-type LI9 inversely correlated with viral load (R = 0.448, P = 0.0485).
  
  
  CONCLUSIONS
  Our results provide support for the role of HLA-B*51-restricted CTLs and functional avidity in the control of early HIV-1 infection.
authors.affiliation: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, UK. nicole.yager@stx.oxon.org
authors.forename: Nicole
authors.initials: N
authors.lastname: Yager
authors.forename: Nicola
authors.initials: N
authors.lastname: Robinson
authors.forename: Helen
authors.initials: H
authors.lastname: Brown
authors.forename: Peter
authors.initials: P
authors.lastname: Flanagan
authors.forename: John
authors.initials: J
authors.lastname: Frater
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Rodney
authors.initials: R
authors.lastname: Phillips
mesh_terms: D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D059949:HLA-B51 Antigen / Q000378:metabolism*; D006801:Humans; D019426:Integrases / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019562:Viral Load; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D018984:Epitopes, T-Lymphocyte; D059949:HLA-B51 Antigen; D012367:RNA, Viral; D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma; D019426:Integrases