Antiviral CD8(+) T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.

TitleAntiviral CD8(+) T Cells Restricted by Human Leukocyte Antigen Class II Exist during Natural HIV Infection and Exhibit Clonal Expansion.
Publication TypeJournal Article
Year of Publication2016
AuthorsRanasinghe S, Lamothe PA, Soghoian DZ, Kazer SW, Cole MB, Shalek AK, Yosef N, R Jones B, Donaghey F, Nwonu C, Jani P, Clayton GM, Crawford F, White J, Montoya A, Power K, Allen TM, Streeck H, Kaufmann DE, Picker LJ, Kappler JW, Walker BD
JournalImmunity
Volume45
Issue4
Pagination917-930
Date Published2016 Oct 18
ISSN1097-4180
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.

DOI10.1016/j.immuni.2016.09.015
Alternate JournalImmunity
PubMed ID27760342
PubMed Central IDPMC5077698
Grant ListP01 AI104715 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
R21 AI125085 / AI / NIAID NIH HHS / United States
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