Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

CD8+TCR bias and immunodominance in HIV-1 infection

Kløverpris, Henrik N., McGregor, Reuben, McLaren, James E., Ladell, Kristin Ingrid, Harndahl, Mikkel, Stryhn, Anette, Carlson, Jonathan M., Koofhethile, Catherine, Gerritsen, Bram, Kesmir, Can, Chen, Fabian, Riddell, Lynn, Luzzi, Graz, Leslie, Alasdair, Walker, Bruce D., Ndung'u, Thumbi, Buus, Søren, Price, David and Goulder, Philip J. 2015. CD8+TCR bias and immunodominance in HIV-1 infection. The Journal of Immunology 194 (11) , pp. 5329-5345. 10.4049/jimmunol.1400854

Full text not available from this repository.

Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: American Association of Immunologists
ISSN: 0022-1767
Date of First Compliant Deposit: 22 August 2017
Date of Acceptance: 25 February 2015
Last Modified: 23 Aug 2017 09:45
URI: http://orca.cf.ac.uk/id/eprint/103829

Citation Data

Cited 11 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item