@article{0172597d95dd4a12b26e77406adc4806,
title = "Antiviral CD8+ T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion",
abstract = "CD8+ T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8+ T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8+ T cells underwent clonal expansion and mediated killing of HIV-infected cells. In one case, these cells comprised 12% of circulating CD8+ T cells, and TCRα analysis revealed two distinct co-expressed TCRα chains, with only one contributing to binding of the class II HLA-peptide complex. These data indicate that class II-restricted CD8+ T cell responses can exist in a chronic human viral infection, and may contribute to immune control.",
keywords = "CD8 T cells, HIV, HLA, MHC class II, TCR, vaccines",
author = "Srinika Ranasinghe and Lamothe, {Pedro A.} and Soghoian, {Damien Z.} and Kazer, {Samuel W.} and Cole, {Michael B.} and Shalek, {Alex K.} and Nir Yosef and Jones, {R. Brad} and Faith Donaghey and Chioma Nwonu and Priya Jani and Clayton, {Gina M.} and Frances Crawford and Janice White and Alana Montoya and Karen Power and Allen, {Todd M.} and Hendrik Streeck and Kaufmann, {Daniel E.} and Picker, {Louis J.} and Kappler, {John W.} and Walker, {Bruce D.}",
note = "Funding Information: We thank all study participants, as well as A. Sette and J. Sidney for the LCL, M.C. Carrington for HLA typing, and M. Nakayama for 5KC mouse hybridomas. This study was funded by the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) grant APP1108533 to L.J.P., B.D.W, and S.R. S.R. is also supported by a CFAR Developmental Award ( NIH/NIAID 5P30AI060354 ). P.A.L. is supported by a HHMI International Student Research Fellowship . D.E.K. is supported by a Research Scholar Career Award of the Quebec Health Research Fund . T.M.A. and K.P. are supported by NIAID grant AI104715 . S.W.K. is supported by a NSF Graduate Research Fellowship . A.K.S. is supported by the Ragon Institute , the Searle Scholars Program , the Beckman Young Investigator Program , the NIH New Innovator Award ( DP2 OD020839 ), and NIH U24 AI11862-01 from NIAID . L.J.P. and OHSU have a significant financial interest in Vir Bio, Inc. , a company that may have a commercial interest in the results of this research and technology. The potential individual and institutional conflicts of interest have been reviewed and are being managed by OHSU. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, U.S. Army, or Department of Defense, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. ",
year = "2016",
month = oct,
day = "18",
doi = "10.1016/j.immuni.2016.09.015",
language = "English (US)",
volume = "45",
pages = "917--930",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "4",
}