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

Srinika Ranasinghe; Pedro A Lamothe; Damien Z Soghoian; Samuel W Kazer; Michael B Cole; Alex K Shalek; Nir Yosef; R Brad Jones; Faith Donaghey; Chioma Nwonu; Priya Jani; Gina M Clayton; Frances Crawford; Janice White; Alana Montoya; Karen Power; Todd M Allen; Hendrik Streeck; Daniel E Kaufmann; Louis J Picker; John W Kappler; Bruce D Walker

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

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

Authors

Srinika Ranasinghe¹, Pedro A Lamothe², Damien Z Soghoian³, Samuel W Kazer⁴, Michael B Cole⁵, Alex K Shalek⁴, Nir Yosef⁶, R Brad Jones⁷, Faith Donaghey³, Chioma Nwonu³, Priya Jani³, Gina M Clayton⁸, Frances Crawford⁸, Janice White⁹, Alana Montoya⁹, Karen Power³, Todd M Allen³, Hendrik Streeck¹⁰, Daniel E Kaufmann¹¹, Louis J Picker¹², John W Kappler⁸, Bruce D Walker¹³

Affiliations

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.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / immunology*
CD8-Positive T-Lymphocytes / immunology*
HIV Infections / immunology*
HLA Antigens / immunology
Histocompatibility Antigens Class II / immunology*
Humans
Receptors, Antigen, T-Cell, alpha-beta / immunology*

Substances

Antiviral Agents
HLA Antigens
Histocompatibility Antigens Class II
Receptors, Antigen, T-Cell, alpha-beta

Abstract

Publication types

MeSH terms

Substances

Grants and funding