Skip NavigationSkip to Content
Return Return to Search Results

HLA class-I-peptide stability mediates CD8+ T cell immunodominance hierarchies and facilitates HLA-associated immune control of HIV

  1. Author:
    Kaseke, Clarety
    Park, Ryan J
    Singh, Nishant K
    Koundakjian, Dylan
    Bashirova,Arman
    Garcia Beltran, Wilfredo F
    Takou Mbah, Overbeck C
    Ma, Jiaqi
    Senjobe, Fernando
    Urbach, Jonathan M
    Nathan, Anusha
    Rossin, Elizabeth J
    Tano-Menka, Rhoda
    Khatri, Ashok
    Piechocka-Trocha, Alicja
    Waring, Michael T
    Birnbaum, Michael E
    Baker, Brian M
    Carrington,Mary
    Walker, Bruce D
    Gaiha, Gaurav D

  2. Author Address

    Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Harvard Radiation Oncology Program, Boston, MA 02114, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA., Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA; Harper Cancer Research Institute, University of Notre Dame, South Bend, IN 46556, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Program in Virology, Harvard Medical School, Boston, MA 02114, USA., Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA; The Broad Institute, Cambridge, MA 02142, USA., Massachusetts General Hospital Endocrine Unit and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research at MIT, Cambridge, MA 02142, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; The Broad Institute, Cambridge, MA 02142, USA; Center for the AIDS Programme of Research in South Africa, Durban 4001, South Africa; Institute for Medical Engineering and Science and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: ggaiha@mgh.harvard.edu.,
    1. Year: 2021
    2. Date: Jul 13
  2. Journal: Cell reports
    1. 36
    2. 2
    3. Pages: 109378
  4. Type of Article: Article
  5. Article Number: 109378
  6. ISSN: 2211-1247
  1. Abstract:

    Defining factors that govern CD8+ T cell immunodominance is critical for the rational design of vaccines for viral pathogens. Here, we assess the contribution of human leukocyte antigen (HLA) class-I-peptide stability for 186 optimal HIV epitopes across 18 HLA alleles using transporter associated with antigen processing (TAP)-deficient mono-allelic HLA-expressing cell lines. We find that immunodominant HIV epitopes increase surface stabilization of HLA class-I molecules in comparison to subdominant epitopes. HLA class-I-peptide stability is also strongly correlated with overall immunodominance hierarchies, particularly for epitopes from high-abundance proteins (e.g., Gag). Moreover, HLA alleles associated with HIV protection are preferentially stabilized by epitopes derived from topologically important viral regions at a greater frequency than neutral and risk alleles. These findings indicate that relative stabilization of HLA class-I is a key factor for CD8+ T cell epitope immunodominance hierarchies, with implications for HIV control and the design of T-cell-based vaccines. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2021.109378
  3. PMID: 34260940
  4. View record in Web of Science®
  5. WOS: 000672741900034
  6. PII : S2211-1247(21)00776-2

Library Notes

  1. Fiscal Year: FY2020-2021
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel