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J Virol. 2015 Oct 21;90(2):650-8. doi: 10.1128/JVI.02123-15.

Cytomegalovirus-Specific CD4 T Cells Are Cytolytic and Mediate Vaccine Protection.

Author information

  • 1Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
  • 2Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.
  • 3Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA benedict@lji.org.

Abstract

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.

IMPORTANCE:

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.

PMID:
26491148
PMCID:
PMC4702662
DOI:
10.1128/JVI.02123-15
[PubMed - indexed for MEDLINE]
Free PMC Article
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