Article open access publication

CD8+ TCR Bias and Immunodominance in HIV-1 Infection

The Journal of Immunology, The American Association of Immunologists, ISSN 0022-1767

Volume 194, 11, 2015

DOI:10.4049/jimmunol.1400854, Dimensions: pub.1079077406, PMC: PMC4433859, PMID: 25911754,

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  1. (1) University of Oxford, grid.4991.5
  2. (2) University of Copenhagen, grid.5254.6, KU
  3. (3) University of KwaZulu-Natal, grid.16463.36
  4. (4) Cardiff University, grid.5600.3
  5. (5) Microsoft Research, eScience Group, Los Angeles, CA 90024;
  6. (6) Utrecht University, grid.5477.1
  7. (7) Royal Berkshire Hospital, grid.416094.e
  8. (8) Northampton General Hospital, grid.416531.4
  9. (9) Wycombe General Hospital, grid.417281.9
  10. (10) Ragon Institute of MGH, MIT and Harvard, grid.461656.6
  11. (11) Max Planck Institute for Infection Biology, grid.418159.0

Description

Immunodominance describes a phenomenon whereby the immune system consistently targets only a fraction of the available Ag pool derived from a given pathogen. In the case of CD8(+) T cells, these constrained epitope-targeting patterns are linked to HLA class I expression and determine disease progression. Despite the biological importance of these predetermined response hierarchies, little is known about the factors that control immunodominance in vivo. In this study, we conducted an extensive analysis of CD8(+) T cell responses restricted by a single HLA class I molecule to evaluate the mechanisms that contribute to epitope-targeting frequency and antiviral efficacy in HIV-1 infection. A clear immunodominance hierarchy was observed across 20 epitopes restricted by HLA-B*42:01, which is highly prevalent in populations of African origin. Moreover, in line with previous studies, Gag-specific responses and targeting breadth were associated with lower viral load set-points. However, peptide-HLA-B*42:01 binding affinity and stability were not significantly linked with targeting frequencies. Instead, immunodominance correlated with epitope-specific usage of public TCRs, defined as amino acid residue-identical TRB sequences that occur in multiple individuals. Collectively, these results provide important insights into a potential link between shared TCR recruitment, immunodominance, and antiviral efficacy in a major human infection.

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Times Cited: 17

Field Citation Ratio (FCR): 2.79

Relative Citation ratio (RCR): 0.73

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