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

Campion, Suzanne L.; Brodie, Tess M.; Fischer, William; Korber, Bette T.; Rossetti, Astrea; Goonetilleke, Nilu; McMichael, Andrew J.; Sallusto, Federica

doi:10.1084/jem.20130555

Back

Journal article

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

Campion, Suzanne L. Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, England, UK
Brodie, Tess M. Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Fischer, William Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545
Korber, Bette T. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545
Rossetti, Astrea Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Goonetilleke, Nilu Department of Microbiology & Immunology, University of North Carolina, Chapel Hill, NC 275994 - Department of Medicine, University of North Carolina, Chapel Hill, NC 27599
McMichael, Andrew J. Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, England, UK
Sallusto, Federica Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland

23.06.2014

Published in:

Journal of experimental medicine. - 2014, vol. 211, no. 7, p. 1273-1280

English 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.

Language