Cytomegalovirus-Specific CD4 T Cells Are Cytolytic and Mediate Vaccine Protection.
CD4 T cells provide protection against cytomegalovirus (CMV) and other persistent viruses, and the ability to quantify and characterize epitope-specific responses is essential to gain a more precise understanding of their effector roles in this regard. Here, we report the first two I-A(d)-restricted CD4 T cell responses specific for mouse CMV (MCMV) epitopes and use a major histocompatibility complex class II (MHC-II) tetramer to characterize their phenotypes and functions. We demonstrate that MCMV-specific CD4 T cells can express high levels of granzyme B and kill target cells in an epitope- and organ-specific manner. In addition, CD4 T cell epitope vaccination of immunocompetent mice reduced MCMV replication in the same organs where CD4 cytotoxic T lymphocyte (CTL) activity was observed. Together, our studies show that MCMV epitope-specific CD4 T cells have the potential to mediate antiviral defense by multiple effector mechanisms in vivo.


OBJECTIVE
CD4 T cells mediate immune protection by using their T cell receptors to recognize specific portions of viral proteins, called epitopes, that are presented by major histocompatibility complex class II (MHC-II) molecules on the surfaces of professional antigen-presenting cells (APCs). In this study, we discovered the first two epitopes derived from mouse cytomegalovirus (MCMV) that are recognized by CD4 T cells in BALB/c mice, a mouse strain commonly used to study the pathogenesis of this virus infection. Here, we report the sequences of these epitopes, characterize the CD4 T cells that recognize them to fight off MCMV infection, and show that we can use the epitopes to vaccinate mice and protect against MCMV.
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Shilpi
S
Verma
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Daniela
D
Weiskopf
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Ankan
A
Gupta
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Bryan
B
McDonald
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Bjoern
B
Peters
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
Alessandro
A
Sette
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA benedict@lji.org.
Chris A
CA
Benedict
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D022482:Cytomegalovirus Vaccines / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D053804:Granzymes / Q000378:metabolism; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D019183:Tombusviridae
D022482:Cytomegalovirus Vaccines; D053804:Granzymes