Proteome-wide analysis of HIV-specific naive and memory CD4+ T cells in unexposed blood donors
Open accessAbstract
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.
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Primed memory T cells may respond to subsequent infections through cross-reactions.
“These primed memory T cells may respond to subsequent infections through cross-reactions [48,52,53].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [48]
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Basic local alignment search tool
Altschul, S. F., Gish, W., Miller, W., Myers, E. W., & Lipman, D. J. (1990) · Journal of Molecular Biology · doi:10.1006/jmbi.1990.9999 · Cited by 98,669 · see citing works
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 20,617 · see citing works
Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand
Rerks‐Ngarm, S., Pitisuttithum, P., Nitayaphan, S., Kaewkungwal, J., Chiu, J., Paris, R., Premsri, N., Namwat, C., de Souza, M. S., Adams, E. M., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0908492 · Cited by 3,036 · see citing works
Keele, B. F., Giorgi, E. E., Salazar-Gonzalez, J. F., Decker, J. M., Pham, K. T., Salazar, M. G., Sun, C., Grayson, T. B., Wang, S., Li, H., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802203105 · Cited by 1,913 · see citing works
Self-citationVigorous HIV-1-Specific CD4 + T Cell Responses Associated with Control of Viremia
Rosenberg, E. S., Billingsley, J. M., Caliendo, A. M., Boswell, S. L., Sax, P. E., Kalams, S. A., & Walker, B. D. (1997) · Science · doi:10.1126/science.278.5342.1447 · Cited by 1,832 · see citing works
Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial
Haynes, B. F., Gilbert, P. B., McElrath, M. J., Zolla‐Pazner, S., Tomaras, G. D., Alam, S. M., Evans, D. T., Montefiori, D. C., Karnasuta, C., Sutthent, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1113425 · Cited by 1,810 · see citing works
HIV preferentially infects HIV-specific CD4+ T cells
Douek, D. C., Brenchley, J. M., Betts, M. R., Ambrozak, D. R., Hill, B. J., Okamoto, Y., Casazza, J. P., Kuruppu, J. C., Kunstman, K., Wolinsky, S. M., et al. (2002) · Nature · doi:10.1038/417095a · Cited by 1,261 · see citing works
Reorganizing the protein space at the Universal Protein Resource (UniProt)
The UniProt Consortium (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr981 · Cited by 1,223 · see citing works
A transposase strategy for creating libraries of circularly permuted proteins
Mehta, M., Liu, S., & Silberg, J. J. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks060 · Cited by 1,042 · see citing works
Moon, J. J., Chu, H., Pepper, M., McSorley, S. J., Jameson, S. C., Kedl, R. M., & Jenkins, M. K. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.007 · Cited by 977 · see citing works
From Vaccines to Memory and Back
Sallusto, F., Lanzavecchia, A., Araki, K., & Ahmed, R. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.008 · Cited by 631 · see citing works
Self-citationDeconstructing the Peptide-MHC Specificity of T Cell Recognition
Birnbaum, M. E., Mendoza, J. L., Sethi, D. K., Dong, S., Glanville, J., Dobbins, J., Özkan, E., Davis, M. M., Wucherpfennig, K. W., & García, K. C. (2014) · Cell · doi:10.1016/j.cell.2014.03.047 · Cited by 558 · see citing works
In Vivo Activation of Antigen-Specific CD4 T Cells
Jenkins, M. K., Khoruts, A., Ingulli, E. G., Mueller, D. L., McSorley, S. J., Reinhardt, R. L., Itano, A. A., & Pape, K. A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.23 · Cited by 512 · see citing works
Ebola haemorrhagic fever in Zaire
Otatume, S. (1996) · Journal of African Studies · doi:10.11619/africa1964.1996.49_95 · Cited by 477 · see citing works
Younes, S., Yassine‐Diab, B., Dumont, A. R., Boulassel, M., Grossman, Z., Routy, J., & Sékaly, R. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20031598 · Cited by 459 · see citing works
Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults
Su, L. F., Kidd, B. A., Han, A., Kotzin, J. J., & Davis, M. M. (2013) · Immunity · doi:10.1016/j.immuni.2012.10.021 · Cited by 429 · see citing works
Limiting Dilution Analysis of Cells in the Immune System
Lefkovits, I., & Waldmann, H. (1979) · Medical Entomology and Zoology · Cited by 374 · see citing works
A Blueprint for HIV Vaccine Discovery
Burton, D. R., Ahmed, R., Barouch, D. H., Butera, S. T., Crotty, S., Godzik, A., Kaufmann, D., McElrath, M. J., Nussenzweig, M. C., Pulendran, B., et al. (2012) · Cell Host & Microbe · doi:10.1016/j.chom.2012.09.008 · Cited by 374 · see citing works
Limiting Dilution Analysis of Cells in the Immune System
Thompson, R. (1980) · Journal of Clinical Pathology · doi:10.1136/jcp.33.6.607-a · Cited by 326 · see citing works
Geiger, R., Duhen, T., Lanzavecchia, A., & Sallusto, F. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090504 · Cited by 207 · see citing works
Self-citationKaufmann, D., Bailey, P. M., Sidney, J., Wagner, B. S., Norris, P. J., Johnston, M. N., Cosimi, L. A., Addo, M. M., Lichterfeld, M. D., Altfeld, M. A., et al. (2004) · Journal of Virology · doi:10.1128/jvi.78.9.4463-4477.2004 · Cited by 176 · see citing works
Kwok, W. W., Tan, V., Gillette, L., Littell, C. T., Soltis, M. A., LaFond, R. E., Yang, J., James, E. A., & DeLong, J. H. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1102190 · Cited by 120 · see citing works
Ranasinghe, S., Flanders, M., Cutler, S., Soghoian, D. Z., Ghebremichael, M. S., Davis, I., Lindqvist, M., Pereyra, F., Walker, B. D., Heckerman, D. E., et al. (2011) · Journal of Virology · doi:10.1128/jvi.05577-11 · Cited by 108 · see citing works
Malavige, G., Jones, L., Black, A., & Ogg, G. (2008) · Clinical and Experimental Immunology · doi:10.1111/j.1365-2249.2008.03633.x · Cited by 83 · see citing works
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Roederer, M., & Koup, R. A. (2003) · Journal of Immunological Methods · doi:10.1016/s0022-1759(02)00423-4 · Cited by 63 · see citing works
Alternative Translational Products and Cryptic T Cell Epitopes: Expecting the Unexpected
Ho, O., & Green, W. R. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.12.8283 · Cited by 52 · see citing works
Limiting dilution analysis of cells of the immune system II: What can be learnt?
Waldmann, H., & Lefkovits, I. (1984) · Immunology Today · doi:10.1016/0167-5699(84)90154-3 · Cited by 44 · see citing works
Ritchie, A. J., Campion, S., Kopycinski, J. T., et al. (2011) · Journal of Virology · doi:10.1128/jvi.02444-10 · Cited by 43 · see citing works
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Bunce, M. (2003) · Humana Press eBooks · doi:10.1385/1-59259-291-0:143 · Cited by 35 · see citing works
Jones, L., Black, A. P., Malavige, G. N., et al. (2007) · European Journal of Immunology · doi:10.1002/eji.200737648 · Cited by 29 · see citing works
Jones, L. O., Black, A. P., Malavige, G. N., et al. (2008) · British Journal of Dermatology · Cited by 18 · see citing works
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Self-citationPeng, Y., Mentzer, A. J., Liu, G., Yao, X., Yin, Z., Dong, D., Dejnirattisai, W., Rostron, T., Supasa, P., Liu, C., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0782-6 · Cited by 1,179 · see citing works
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Bacher, P., Rosati, E., Esser, D., Martini, G. R., Saggau, C., Schiminsky, E., Dargvainiene, J., Schröder, I., Wieters, I., Khodamoradi, Y., et al. (2020) · Immunity · doi:10.1016/j.immuni.2020.11.016 · Cited by 314 · see citing works
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- Authors
- Campion, S. L., Brodie, T. M., Fischer, W., Korber, B. T., Rossetti, A., Goonetilleke, N., McMichael, A. J., & Sallusto, F.
- Affiliations
- University of Oxford (GB)
- Institute for Research in Biomedicine (CH)
- Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, NM 87545 3
- Los Alamos National Laboratory (US)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Campion, Suzanne L.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2014-06-23
- Volume
- 211
- Issue
- 7
- Pages
- 1273-1280
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4076590
- OpenAlex
- W2105492553
- Cited by
- 84
- References
- 31
- Citations by year
- 2026: 2 · 2024: 2 · 2023: 6 · 2022: 9 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 4 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 8
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- reroDoc Digital Library (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- UNC Libraries
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (147662)
- National Institutes of Health (HHSN272201300006C), AI-100645)
- Medical Research Council (MR/K012037/1)
- National Institute of Allergy and Infectious Diseases (AI-100645, HHSN-272201300006C, UM1AI100645, P30AI027763)
- Topics
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- CD4+ T cells, naive T cells, central memory T cells, effector memory T cells, epitope mapping, cross-reactivity, immunodominance
- MeSH terms
- Antigens, Viral, Cross Reactions, Female, Humans, Immunologic Memory, Male, Peptides, Viral Proteins, CD4-Positive T-Lymphocytes, HIV-1, AIDS Vaccines, Epitopes, T-Lymphocyte, Proteome, Microbiota
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