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Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells
The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933048/ https://www.ncbi.nlm.nih.gov/pubmed/29302013 http://dx.doi.org/10.1126/science.aam8825 |
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| author | Ramsuran, Veron Naranbhai, Vivek Horowitz, Amir Qi, Ying Martin, Maureen P. Yuki, Yuko Gao, Xiaojiang Walker-Sperling, Victoria Del Prete, Gregory Q. Schneider, Douglas K. Lifson, Jeffrey D. Fellay, Jacques Deeks, Steven G. Martin, Jeffrey N. Goedert, James J. Wolinsky, Steven M. Michael, Nelson L. Kirk, Gregory D. Buchbinder, Susan Haas, David Ndung’u, Thumbi Goulder, Philip Parham, Peter Walker, Bruce D. Carlson, Jonathan M. Carrington, Mary |
| author_facet | Ramsuran, Veron Naranbhai, Vivek Horowitz, Amir Qi, Ying Martin, Maureen P. Yuki, Yuko Gao, Xiaojiang Walker-Sperling, Victoria Del Prete, Gregory Q. Schneider, Douglas K. Lifson, Jeffrey D. Fellay, Jacques Deeks, Steven G. Martin, Jeffrey N. Goedert, James J. Wolinsky, Steven M. Michael, Nelson L. Kirk, Gregory D. Buchbinder, Susan Haas, David Ndung’u, Thumbi Goulder, Philip Parham, Peter Walker, Bruce D. Carlson, Jonathan M. Carrington, Mary |
| author_sort | Ramsuran, Veron |
| collection | PubMed |
| description | The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A–derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease. |
| format | Online Article Text |
| id | pubmed-5933048 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-59330482018-07-05 Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells Ramsuran, Veron Naranbhai, Vivek Horowitz, Amir Qi, Ying Martin, Maureen P. Yuki, Yuko Gao, Xiaojiang Walker-Sperling, Victoria Del Prete, Gregory Q. Schneider, Douglas K. Lifson, Jeffrey D. Fellay, Jacques Deeks, Steven G. Martin, Jeffrey N. Goedert, James J. Wolinsky, Steven M. Michael, Nelson L. Kirk, Gregory D. Buchbinder, Susan Haas, David Ndung’u, Thumbi Goulder, Philip Parham, Peter Walker, Bruce D. Carlson, Jonathan M. Carrington, Mary Science Article The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A–derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease. 2018-01-04 2018-01-05 /pmc/articles/PMC5933048/ /pubmed/29302013 http://dx.doi.org/10.1126/science.aam8825 Text en This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material. http://www.sciencemag.org/help/reprints-and-permissions |
| spellingShingle | Article Ramsuran, Veron Naranbhai, Vivek Horowitz, Amir Qi, Ying Martin, Maureen P. Yuki, Yuko Gao, Xiaojiang Walker-Sperling, Victoria Del Prete, Gregory Q. Schneider, Douglas K. Lifson, Jeffrey D. Fellay, Jacques Deeks, Steven G. Martin, Jeffrey N. Goedert, James J. Wolinsky, Steven M. Michael, Nelson L. Kirk, Gregory D. Buchbinder, Susan Haas, David Ndung’u, Thumbi Goulder, Philip Parham, Peter Walker, Bruce D. Carlson, Jonathan M. Carrington, Mary Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells |
| title | Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells |
| title_full | Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells |
| title_fullStr | Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells |
| title_full_unstemmed | Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells |
| title_short | Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells |
| title_sort | elevated hla-a expression impairs hiv control through inhibition of nkg2a-expressing cells |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933048/ https://www.ncbi.nlm.nih.gov/pubmed/29302013 http://dx.doi.org/10.1126/science.aam8825 |
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