title: Escape is a more common mechanism than avidity reduction for evasion of CD8+ T cell responses in primary human immunodeficiency virus type 1 infection.
abstract: BACKGROUND
  CD8+ T cells play an important role in control of viral replication during acute and early human immunodeficiency virus type 1 (HIV-1) infection, contributing to containment of the acute viral burst and establishment of the prognostically-important persisting viral load. Understanding mechanisms that impair CD8+ T cell-mediated control of HIV replication in primary infection is thus of importance. This study addressed the relative extent to which HIV-specific T cell responses are impacted by viral mutational escape versus reduction in response avidity during the first year of infection.
  
  
  RESULTS
  18 patients presenting with symptomatic primary HIV-1 infection, most of whom subsequently established moderate-high persisting viral loads, were studied. HIV-specific T cell responses were mapped in each individual and responses to a subset of optimally-defined CD8+ T cell epitopes were followed from acute infection onwards to determine whether they were escaped or declined in avidity over time. During the first year of infection, sequence variation occurred in/around 26/33 epitopes studied (79%). In 82% of cases of intra-epitopic sequence variation, the mutation was confirmed to confer escape, although T cell responses were subsequently expanded to variant sequences in some cases. In contrast, < 10% of responses to index sequence epitopes declined in functional avidity over the same time-frame, and a similar proportion of responses actually exhibited an increase in functional avidity during this period.
  
  
  CONCLUSIONS
  Escape appears to constitute a much more important means of viral evasion of CD8+ T cell responses in acute and early HIV infection than decline in functional avidity of epitope-specific T cells. These findings support the design of vaccines to elicit T cell responses that are difficult for the virus to escape.
authors.affiliation: Nuffield Department of Clinical Medicine, University of Oxford, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DS, UK. persephone.borrow@ndm.ox.ac.uk.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Turnbull
authors.forename: Joshua
authors.initials: J
authors.lastname: Baalwa
authors.forename: Karen E
authors.initials: KE
authors.lastname: Conrod
authors.forename: Shuyi
authors.initials: S
authors.lastname: Wang
authors.forename: Xiping
authors.initials: X
authors.lastname: Wei
authors.forename: Mailee
authors.initials: M
authors.lastname: Wong
authors.forename: Joanna
authors.initials: J
authors.lastname: Turner
authors.forename: Pierre
authors.initials: P
authors.lastname: Pellegrino
authors.forename: Ian
authors.initials: I
authors.lastname: Williams
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D020125:Mutation, Missense; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D014764:Viral Proteins