TY - JOUR
T1 - HLA tapasin independence
T2 - broader peptide repertoire and HIV control
AU - Bashirova, Arman A.
AU - Viard, Mathias
AU - Naranbhai, Vivek
AU - Grifoni, Alba
AU - Garcia-Beltran, Wilfredo
AU - Akdag, Marjan
AU - Yuki, Yuko
AU - Gao, Xiaojiang
AU - O’hUigin, Colm
AU - Raghavan, Malini
AU - Wolinsky, Steven
AU - Bream, Jay H.
AU - Duggal, Priya
AU - Martinson, Jeremy
AU - Michael, Nelson L.
AU - Kirk, Gregory D.
AU - Buchbinder, Susan P.
AU - Haas, David
AU - Goedert, James J.
AU - Deeks, Steven G.
AU - Fellay, Jacques
AU - Walker, Bruce
AU - Goulder, Philip
AU - Cresswell, Peter
AU - Elliott, Tim
AU - Sette, Alessandro
AU - Carlson, Jonathan
AU - Carrington, Mary
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank Drs. George Nelson and Maureen P. Martin for helpful discussions. We also thank the volunteers in the contributing cohorts, their health care providers, and the investigators involved in data collection. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under Contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH), Frederick National Laboratory, Center for Cancer Research. A.S. was supported by NIH Grants HHSN272201400045C and 75N93019C00001. M.R. was supported by National Institute of Allergy and Infectious Diseases/NIH Grant R01AI044115. See the extended acknowledgments in SI Appendix for full details.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/11/10
Y1 - 2020/11/10
N2 - Human leukocyte antigen (HLA) class I allotypes vary in thei ability to present peptides in the absence of tapasin, an essentia component of the peptide loading complex. We quantified tapasi dependence of all allotypes that are common in European an African Americans (n = 97), which revealed a broad continuum o values. Ex vivo examination of cytotoxic T cell responses to th entire HIV-1 proteome from infected subjects indicates tha tapasin-dependent allotypes present a more limited set of distinc peptides than do tapasin-independent allotypes, data supporte by computational predictions. This suggests that variation in tapa sin dependence may impact the strength of the immune response by altering peptide repertoire size. In support of this model, w observed that individuals carrying HLA class I genotypes charac terized by greater tapasin independence progress more slowly t AIDS and maintain lower viral loads, presumably due to increase breadth of peptide presentation. Thus, tapasin dependence level like HLA zygosity, may serve as a means to restrict or expan breadth of the HLA-I peptide repertoire across humans, ultimatel influencing immune responses to pathogens and vaccines.
AB - Human leukocyte antigen (HLA) class I allotypes vary in thei ability to present peptides in the absence of tapasin, an essentia component of the peptide loading complex. We quantified tapasi dependence of all allotypes that are common in European an African Americans (n = 97), which revealed a broad continuum o values. Ex vivo examination of cytotoxic T cell responses to th entire HIV-1 proteome from infected subjects indicates tha tapasin-dependent allotypes present a more limited set of distinc peptides than do tapasin-independent allotypes, data supporte by computational predictions. This suggests that variation in tapa sin dependence may impact the strength of the immune response by altering peptide repertoire size. In support of this model, w observed that individuals carrying HLA class I genotypes charac terized by greater tapasin independence progress more slowly t AIDS and maintain lower viral loads, presumably due to increase breadth of peptide presentation. Thus, tapasin dependence level like HLA zygosity, may serve as a means to restrict or expan breadth of the HLA-I peptide repertoire across humans, ultimatel influencing immune responses to pathogens and vaccines.
KW - HLA | tapasin | peptide repertoire
UR - http://www.scopus.com/inward/record.url?scp=85096079764&partnerID=8YFLogxK
U2 - 10.1073/pnas.2013554117
DO - 10.1073/pnas.2013554117
M3 - Article
C2 - 33097667
AN - SCOPUS:85096079764
SN - 0027-8424
VL - 117
SP - 28232
EP - 28238
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 45
ER -