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: Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, England, UK Suzanne.Campion@ndm.ox.ac.uk.
authors: Suzanne L
authors: SL
authors: Campion
authors: Institute for Research in Biomedicine (IRB), 6-CH-6500 Bellinzona, Switzerland.
authors: Tess M
authors: TM
authors: Brodie
authors: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545.
authors: William
authors: W
authors: Fischer
authors: Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545.
authors: Bette T
authors: BT
authors: Korber
authors: Institute for Research in Biomedicine (IRB), 6-CH-6500 Bellinzona, Switzerland.
authors: Astrea
authors: A
authors: Rossetti
authors: Department of Microbiology & Immunology and Department of Medicine, University of North Carolina, Chapel Hill, NC 27599 Department of Microbiology & Immunology and Department of Medicine, University of North Carolina, Chapel Hill, NC 27599.
authors: Nilu
authors: N
authors: Goonetilleke
authors: Nuffield Department of Medicine Research Building, University of Oxford, Old Road Campus, Headington, Oxford OX3 7FZ, England, UK.
authors: Andrew J
authors: AJ
authors: McMichael
authors: Institute for Research in Biomedicine (IRB), 6-CH-6500 Bellinzona, Switzerland.
authors: Federica
authors: F
authors: Sallusto
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D064307:Microbiota / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D020543:Proteome / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D020543:Proteome; D014764:Viral Proteins