Title: Proteome-wide analysis of HIV-specific naive and memory CD4⁺ T cells in unexposed blood donors

Abstract

The preexisting HIV-1–specific T cell repertoire must influence both the immunodominance of T cells after infection and immunogenicity of vaccines. We directly compared two methods for measuring the preexisting CD4⁺ T cell repertoire in healthy HIV-1–negative volunteers, the HLA-peptide tetramer enrichment and T cell library technique, and show high concordance (r = 0.989). Using the library technique, we examined whether naive, central memory, and/or effector memory CD4⁺ T cells specific for overlapping peptides spanning the entire HIV-1 proteome were detectable in 10 HLA diverse, HIV-1–unexposed, seronegative donors. HIV-1–specific cells were detected in all donors at a mean of 55 cells/million naive cells and 38.9 and 34.1 cells/million in central and effector memory subsets. Remarkably, peptide mapping showed most epitopes recognized by naive (88%) and memory (56%) CD4⁺ T cells had been previously reported in natural HIV-1 infection. Furthermore, 83% of epitopes identified in preexisting memory subsets shared epitope length matches (8–12 amino acids) with human microbiome proteins, suggestive of a possible cross-reactive mechanism. These results underline the power of a proteome-wide analysis of peptide recognition by human T cells for the identification of dominant antigens and provide a baseline for optimizing HIV-1–specific helper cell responses by vaccination.

Authors:

Campion, Suzanne L. ^[1]; Brodie, Tess M. ^[2]; Fischer, William ^[3]; Korber, Bette T. ^[3]; Rossetti, Astrea ^[2]; Goonetilleke, Nilu ^[4]; McMichael, Andrew J. ^[1]; Sallusto, Federica ^[2]

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+ Show Author Affiliations

1. University of Oxford (United Kingdom)
2. Institute for Research in Biomedicine (IRB), Bellinzona (Switzerland)
3. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
4. University of North Carolina, Chapel Hill, NC (United States)

Publication Date:

Mon Jun 23 00:00:00 EDT 2014

Research Org.:

Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Org.:

USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery; European Research Council (ERC)

OSTI Identifier:

1625198

Grant/Contract Number:  

AC52-06NA25396; UM1-AI100645-01; ERC-2012-ADG-2012314; CRSII3_147662

Resource Type:

Accepted Manuscript

Journal Name:

Journal of Experimental Medicine

Additional Journal Information:

Journal Volume: 211; Journal Issue: 7; Journal ID: ISSN 0022-1007

Publisher:

Rockefeller University Press

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; basic local alignment sequence tool; glycoprotein E; human microbiome project; immediate early phosphoprotein 63; Los Alamos National Laboratory; tetanus toxoid; varicella zoster virus.