PMID- 33097667
OWN - NLM
STAT- MEDLINE
DCOM- 20210104
LR  - 20231130
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 117
IP  - 45
DP  - 2020 Nov 10
TI  - HLA tapasin independence: broader peptide repertoire and HIV control.
PG  - 28232-28238
LID - 10.1073/pnas.2013554117 [doi]
AB  - 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.
CI  - Copyright (c) 2020 the Author(s). Published by PNAS.
FAU - Bashirova, Arman A
AU  - Bashirova AA
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702.
FAU - Viard, Mathias
AU  - Viard M
AUID- ORCID: 0000-0002-1737-8021
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702.
FAU - Naranbhai, Vivek
AU  - Naranbhai V
AUID- ORCID: 0000-0003-4281-8882
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215.
FAU - Grifoni, Alba
AU  - Grifoni A
AUID- ORCID: 0000-0002-2209-5966
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 
      92037.
FAU - Garcia-Beltran, Wilfredo
AU  - Garcia-Beltran W
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139.
FAU - Akdag, Marjan
AU  - Akdag M
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702.
FAU - Yuki, Yuko
AU  - Yuki Y
AUID- ORCID: 0000-0003-1721-6003
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702.
FAU - Gao, Xiaojiang
AU  - Gao X
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702.
FAU - O'hUigin, Colm
AU  - O'hUigin C
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702.
FAU - Raghavan, Malini
AU  - Raghavan M
AUID- ORCID: 0000-0002-1345-9318
AD  - Department of Microbiology and Immunology, University of Michigan Medical School, 
      Ann Arbor, MI 48109.
FAU - Wolinsky, Steven
AU  - Wolinsky S
AD  - Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern 
      University, Chicago, IL 60611.
FAU - Bream, Jay H
AU  - Bream JH
AUID- ORCID: 0000-0002-9149-7643
AD  - Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, MD 21205.
FAU - Duggal, Priya
AU  - Duggal P
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, MD 21205.
FAU - Martinson, Jeremy
AU  - Martinson J
AUID- ORCID: 0000-0003-4673-7238
AD  - Department of Infectious Diseases and Microbiology, University of Pittsburgh 
      Graduate School of Public Health, Pittsburgh, PA 15261.
FAU - Michael, Nelson L
AU  - Michael NL
AD  - US Military HIV Research Program, Walter Reed Army Institute of Research, Silver 
      Spring, MD 20910.
FAU - Kirk, Gregory D
AU  - Kirk GD
AD  - Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 
      Baltimore, MD 21205.
FAU - Buchbinder, Susan P
AU  - Buchbinder SP
AD  - HIV Research Section, San Francisco Department of Public Health, San Francisco, 
      CA 94102.
FAU - Haas, David
AU  - Haas D
AD  - Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, 
      TN 37204.
FAU - Goedert, James J
AU  - Goedert JJ
AD  - Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and 
      Genetics, National Cancer Institute, National Institutes of Health, Rockville, MD 
      20850.
FAU - Deeks, Steven G
AU  - Deeks SG
AD  - Department of Medicine, University of California, San Francisco, CA 94110.
FAU - Fellay, Jacques
AU  - Fellay J
AUID- ORCID: 0000-0002-8240-939X
AD  - School of Life Sciences, Ecole Polytechnique Federale de Lausanne, 1015 Lausanne, 
      Switzerland.
AD  - Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland.
FAU - Walker, Bruce
AU  - Walker B
AUID- ORCID: 0000-0001-6122-9245
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139.
FAU - Goulder, Philip
AU  - Goulder P
AD  - Department of Paediatrics, University of Oxford, Oxford, OX1 4AJ, United Kingdom.
FAU - Cresswell, Peter
AU  - Cresswell P
AUID- ORCID: 0000-0003-0540-2351
AD  - Department of Immunobiology, Yale University School of Medicine, New Haven, CT 
      06520.
FAU - Elliott, Tim
AU  - Elliott T
AUID- ORCID: 0000-0003-1097-0222
AD  - Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, 
      United Kingdom.
AD  - Centre for Cancer Immunology, University of Southampton, Southampton SO16 6YD, 
      United Kingdom.
FAU - Sette, Alessandro
AU  - Sette A
AD  - Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 
      92037.
AD  - Department of Medicine, University of California San Diego, La Jolla, CA 92093.
FAU - Carlson, Jonathan
AU  - Carlson J
AD  - Immunomics, Microsoft Healthcare NExT, Redmond, WA 98052.
FAU - Carrington, Mary
AU  - Carrington M
AUID- ORCID: 0000-0002-2692-2180
AD  - Basic Science Program, Frederick National Laboratory for Cancer Research, 
      Frederick, MD 21702; carringm@mail.nih.gov.
AD  - Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of 
      Technology and Harvard University, Cambridge, MA 02139.
LA  - eng
GR  - R01 AI044115/AI/NIAID NIH HHS/United States
GR  - R01 AI133673/AI/NIAID NIH HHS/United States
GR  - 75N93019C00001/AI/NIAID NIH HHS/United States
GR  - HHSN272201400045C/AI/NIAID NIH HHS/United States
GR  - P30 AI027763/AI/NIAID NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - U01 HL146240/HL/NHLBI NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - UM1 AI068636/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20201023
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Human Immunodeficiency Virus Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Peptides)
RN  - 0 (tapasin)
SB  - IM
CIN - Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):31570-31572. PMID: 33239443
MH  - Antigen Presentation/*genetics
MH  - *HIV Infections/genetics/immunology
MH  - HIV-1/immunology
MH  - *Histocompatibility Antigens Class I/genetics/immunology/metabolism
MH  - Human Immunodeficiency Virus Proteins/immunology
MH  - Humans
MH  - *Membrane Transport Proteins/genetics/immunology/metabolism
MH  - Peptides/immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Viral Load/genetics/immunology
PMC - PMC7668082
OTO - NOTNLM
OT  - HLA
OT  - peptide repertoire
OT  - tapasin
COIS- The authors declare no competing interest.
EDAT- 2020/10/25 06:00
MHDA- 2021/01/05 06:00
PMCR- 2020/10/23
CRDT- 2020/10/24 05:29
PHST- 2020/10/25 06:00 [pubmed]
PHST- 2021/01/05 06:00 [medline]
PHST- 2020/10/24 05:29 [entrez]
PHST- 2020/10/23 00:00 [pmc-release]
AID - 2013554117 [pii]
AID - 202013554 [pii]
AID - 10.1073/pnas.2013554117 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28232-28238. doi: 
      10.1073/pnas.2013554117. Epub 2020 Oct 23.