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.
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA. Electronic address: sranasinghe@mgh.harvard.edu.
authors.forename: Srinika
authors.initials: S
authors.lastname: Ranasinghe
authors.affiliation: 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.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Lamothe
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
authors.forename: Damien Z
authors.initials: DZ
authors.lastname: Soghoian
authors.affiliation: 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.
authors.forename: Samuel W
authors.initials: SW
authors.lastname: Kazer
authors.affiliation: Department of Physics, University of California, Berkeley, CA 94720, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Cole
authors.affiliation: 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.
authors.forename: Alex K
authors.initials: AK
authors.lastname: Shalek
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; Department of Physics, University of California, Berkeley, CA 94720, USA.
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA; George Washington University, Washington, DC 20052, USA.
authors.forename: R Brad
authors.initials: RB
authors.lastname: Jones
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
authors.forename: Faith
authors.initials: F
authors.lastname: Donaghey
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
authors.forename: Chioma
authors.initials: C
authors.lastname: Nwonu
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Jani
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Clayton
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Frances
authors.initials: F
authors.lastname: Crawford
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Janice
authors.initials: J
authors.lastname: White
authors.affiliation: Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
authors.forename: Alana
authors.initials: A
authors.lastname: Montoya
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Power
authors.affiliation: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 01239, USA.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: 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.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Streeck
authors.affiliation: 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.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Kaufmann
authors.affiliation: Vaccine and Gene Therapy Institute and Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Picker
authors.affiliation: Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Biomedical Research, National Jewish Health, Denver, CO 80206, USA.
authors.forename: John W
authors.initials: JW
authors.lastname: Kappler
authors.affiliation: 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.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D000998:Antiviral Agents / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
chemical_list: D000998:Antiviral Agents; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta
keywords: CD8(+) T cells; HIV; HLA; MHC class II; TCR; vaccines