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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 b...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668082/ https://www.ncbi.nlm.nih.gov/pubmed/33097667 http://dx.doi.org/10.1073/pnas.2013554117 |
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author | 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 Carrington, Mary |
author_facet | 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 Carrington, Mary |
author_sort | Bashirova, Arman A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7668082 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-76680822020-11-27 HLA tapasin independence: broader peptide repertoire and HIV control 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 Carrington, Mary Proc Natl Acad Sci U S A Biological Sciences 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. National Academy of Sciences 2020-11-10 2020-10-23 /pmc/articles/PMC7668082/ /pubmed/33097667 http://dx.doi.org/10.1073/pnas.2013554117 Text en Copyright © 2020 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Biological Sciences 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 Carrington, Mary HLA tapasin independence: broader peptide repertoire and HIV control |
title | HLA tapasin independence: broader peptide repertoire and HIV control |
title_full | HLA tapasin independence: broader peptide repertoire and HIV control |
title_fullStr | HLA tapasin independence: broader peptide repertoire and HIV control |
title_full_unstemmed | HLA tapasin independence: broader peptide repertoire and HIV control |
title_short | HLA tapasin independence: broader peptide repertoire and HIV control |
title_sort | hla tapasin independence: broader peptide repertoire and hiv control |
topic | Biological Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668082/ https://www.ncbi.nlm.nih.gov/pubmed/33097667 http://dx.doi.org/10.1073/pnas.2013554117 |
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