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Immunity. 2016 Oct 18;45(4):917-930. doi: 10.1016/j.immuni.2016.09.015.

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

Author information

1
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA. Electronic address: sranasinghe@mgh.harvard.edu.
2
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
3
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
4
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 01239, USA; Broad Institute, Cambridge, MA 01239, USA.
5
Department of Physics, University of California, Berkeley, CA 94720, USA.
6
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Department of Physics, University of California, Berkeley, CA 94720, USA.
7
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; George Washington University, Washington, DC 20052, USA.
8
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
9
Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
10
Institute for HIV Research, University Hospital, University Duisburg-Essen, Essen 45147, Germany; U.S. Military HIV Research Program, Henry M. Jackson Foundation, Rockville, MD 20910, USA.
11
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Centre de Recherche du Centre hospitalier de l'Université de Montréal, Montreal, QC H2X 3J4, Canada.
12
Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
13
Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 01239, USA; Broad Institute, Cambridge, MA 01239, USA. Electronic address: bwalker@mgh.harvard.edu.

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

PMID:
27760342
PMCID:
PMC5077698
DOI:
10.1016/j.immuni.2016.09.015
[Indexed for MEDLINE]
Free PMC Article

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