HLA tapasin independence: broader peptide repertoire and HIV control.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_2878DD324F2A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HLA tapasin independence: broader peptide repertoire and HIV control.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Bashirova A.A., Viard M., Naranbhai V., Grifoni A., Garcia-Beltran W., Akdag M., Yuki Y., Gao X., O'hUigin C., Raghavan M., Wolinsky S., Bream J.H., Duggal P., Martinson J., Michael N.L., Kirk G.D., Buchbinder S.P., Haas D., Goedert J.J., Deeks S.G., Fellay J., Walker B., Goulder P., Cresswell P., Elliott T., Sette A., Carlson J., Carrington M.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
10/11/2020
Peer-reviewed
Oui
Volume
117
Number
45
Pages
28232-28238
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Keywords
HLA, peptide repertoire, tapasin
Pubmed
Open Access
Yes
Create date
02/11/2020 13:17
Last modification date
30/04/2021 6:09
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