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HLA tapasin independence: broader peptide repertoire and HIV control

  1. Author:
    Bashirova,Arman
    Viard,Mathias [ORCID]
    Naranbhai, Vivek [ORCID]
    Grifoni, Alba [ORCID]
    Garcia-Beltran, Wilfredo
    Akdag,Marjan
    Yuki,Yuko [ORCID]
    Gao,Xiaojiang
    O'hUigin, Colm
    Raghavan, Malini [ORCID]
    Wolinsky, Steven
    Bream, Jay H [ORCID]
    Duggal, Priya
    Martinson, Jeremy [ORCID]
    Michael, Nelson L
    Kirk, Gregory D
    Buchbinder, Susan P
    Haas, David
    Goedert, James J
    Deeks, Steven G
    Fellay, Jacques [ORCID]
    Walker, Bruce [ORCID]
    Goulder, Philip
    Cresswell, Peter [ORCID]
    Elliott, Tim [ORCID]
    Sette, Alessandro
    Carlson, Jonathan
    Carrington,Mary [ORCID]

  2. Author Address

    Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702., Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215., Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037., Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139., Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109., Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611., Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205., Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205., Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15261., US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910., HIV Research Section, San Francisco Department of Public Health, San Francisco, CA 94102., Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37204., Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 20850., Department of Medicine, University of California, San Francisco, CA 94110., School of Life Sciences, 201;cole Polytechnique F 233;d 233;rale de Lausanne, 1015 Lausanne, Switzerland., Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland., Department of Paediatrics, University of Oxford, Oxford, OX1 4AJ, United Kingdom., Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520., Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, United Kingdom., Centre for Cancer Immunology, University of Southampton, Southampton SO16 6YD, United Kingdom., Department of Medicine, University of California San Diego, La Jolla, CA 92093., Immunomics, Microsoft Healthcare NExT, Redmond, WA 98052., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702; carringm@mail.nih.gov.,
    1. Year: 2020
    2. Date: NOV 10
    3. Epub Date: 2020 10 23
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 117
    2. 45
    3. Pages: 28232-28238
  4. Type of Article: Article
  5. ISSN: 0027-8424
  1. Abstract:

    Human leukocyte antigen (HLA) class I allotypes vary in their ability to present peptides in the absence of tapasin, an essential component of the peptide loading complex. We quantified tapasin dependence of all allotypes that are common in European and African Americans (n = 97), which revealed a broad continuum of values. Ex vivo examination of cytotoxic T cell responses to the entire HIV-1 proteome from infected subjects indicates that tapasin-dependent allotypes present a more limited set of distinct peptides than do tapasin-independent allotypes, data supported by computational predictions. This suggests that variation in tapasin dependence may impact the strength of the immune responses by altering peptide repertoire size. In support of this model, we observed that individuals carrying HLA class I genotypes characterized by greater tapasin independence progress more slowly to AIDS and maintain lower viral loads, presumably due to increased breadth of peptide presentation. Thus, tapasin dependence level, like HLA zygosity, may serve as a means to restrict or expand breadth of the HLA-I peptide repertoire across humans, ultimately influencing immune responses to pathogens and vaccines. Copyright © 2020 the Author(s). Published by PNAS.

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External Sources

  1. View Full Text
  2. DOI: 10.1073/pnas.2013554117
  3. PMID: 33097667
  4. View record in Web of Science®
  5. WOS: 000590745300007
  6. PII : 2013554117

Library Notes

  1. Fiscal Year: FY2020-2021
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