Campion, Suzanne L. Brodie, Tess M. Fischer, William Korber, Bette T. Rossetti, Astrea Goonetilleke, Nilu McMichael, Andrew J. Sallusto, Federica 2014-06-23 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. application/pdf https://susi.usi.ch/global/documents/318830 https://localhost:5000/ark:/12658/srd1318830 https://susi.usi.ch/documents/318830/files/Campion_JEM_2014.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1084/jem.20130555 info:eu-repo/semantics/altIdentifier/ark/12658/srd1318830 info:eu-repo/semantics/openAccess CC BY-NC-SA Journal of experimental medicine. - 2014, vol. 211, no. 7, p. 1273-1280 info:eu-repo/classification/udc/61 Proteome-wide analysis of HIV-specific naive and memory CD4+ T cells in unexposed blood donors http://purl.org/coar/resource_type/c_6501