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HLA tapasin independence: broader peptide repertoire and HIV control

HLA tapasin independence: broader peptide repertoire and HIV control
HLA tapasin independence: broader peptide repertoire and HIV control

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.

HLA, peptide repertoire, tapasin
0027-8424
28232-28238
Bashirova, Arman A
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Viard, Mathias
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Naranbhai, Vivek
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Grifoni, Alba
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Garcia-Beltran, Wilfredo
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Akdag, Marjan
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Yuki, Yuko
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Gao, Xiaojiang
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O'hUigin, Colm
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Raghavan, Malini
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Wolinsky, Steven
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Bream, Jay H.
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Duggal, Priya
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Martinson, Jeremy
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Michael, Nelson L.
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Kirk, Gregory D.
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Buchbinder, Susan P.
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Haas, David
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Goedert, James J.
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Deeks, Steven G.
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Fellay, Jacques
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Walker, Bruce
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Goulder, Philip
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Cresswell, Peter
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Elliott, Tim
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Sette, Alessandro
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Carlson, Jonathan
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Carrington, Mary
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Bashirova, Arman A
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Viard, Mathias
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Naranbhai, Vivek
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Grifoni, Alba
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Garcia-Beltran, Wilfredo
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Akdag, Marjan
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Yuki, Yuko
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Gao, Xiaojiang
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O'hUigin, Colm
b27e26e7-e437-411f-88b9-2f34d60934e4
Raghavan, Malini
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Wolinsky, Steven
80a24f0f-f7c2-4441-aab8-51ad7e7cb23b
Bream, Jay H.
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Duggal, Priya
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Martinson, Jeremy
13690753-3c6b-4e0d-b496-f524c3d98597
Michael, Nelson L.
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Kirk, Gregory D.
562ddcaa-f2c2-4e06-b87e-08e99b0e1244
Buchbinder, Susan P.
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Haas, David
d23548e1-321a-4863-8072-29b0188b8658
Goedert, James J.
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Deeks, Steven G.
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Fellay, Jacques
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Walker, Bruce
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Goulder, Philip
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Cresswell, Peter
d577d2b1-60aa-45bf-88aa-522afe2f6467
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Sette, Alessandro
240988b3-3c05-4041-a39b-8be8e145803c
Carlson, Jonathan
8857d204-603d-4757-a6f1-0c1202ae8f8d
Carrington, Mary
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Bashirova, Arman A, Viard, Mathias, Naranbhai, Vivek, Grifoni, Alba, Garcia-Beltran, Wilfredo, Akdag, Marjan, Yuki, Yuko, Gao, Xiaojiang, O'hUigin, Colm, Raghavan, Malini, Wolinsky, Steven, Bream, Jay H., Duggal, Priya, Martinson, Jeremy, Michael, Nelson L., Kirk, Gregory D., Buchbinder, Susan P., Haas, David, Goedert, James J., Deeks, Steven G., Fellay, Jacques, Walker, Bruce, Goulder, Philip, Cresswell, Peter, Elliott, Tim, Sette, Alessandro, Carlson, Jonathan and Carrington, Mary (2020) HLA tapasin independence: broader peptide repertoire and HIV control. Proceedings of the National Academy of Sciences of the United States of America, 117 (45), 28232-28238. (doi:10.1073/pnas.2013554117).

Record type: Article

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.

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2013554117.full - Version of Record
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More information

Accepted/In Press date: 8 September 2020
e-pub ahead of print date: 23 October 2020
Additional Information: Copyright © 2020 the Author(s). Published by PNAS.
Keywords: HLA, peptide repertoire, tapasin

Identifiers

Local EPrints ID: 444750
URI: http://eprints.soton.ac.uk/id/eprint/444750
ISSN: 0027-8424
PURE UUID: 75d5c8e8-b702-4324-bd8e-4b929670742b
ORCID for Tim Elliott: ORCID iD orcid.org/0000-0003-1097-0222

Catalogue record

Date deposited: 03 Nov 2020 17:31
Last modified: 28 Apr 2022 01:48

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Contributors

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

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