Impact of regulated secretion on antiparasitic CD8 T cell responses

Cell Rep. 2014 Jun 12;7(5):1716-1728. doi: 10.1016/j.celrep.2014.04.031. Epub 2014 May 22.

Abstract

CD8 T cells play a key role in defense against the intracellular parasite Toxoplasma, but why certain CD8 responses are more potent than others is not well understood. Here, we describe a parasite antigen, ROP5, that elicits a CD8 T cell response in genetically susceptible mice. ROP5 is secreted via parasite organelles termed rhoptries that are injected directly into host cells during invasion, whereas the protective, dense-granule antigen GRA6 is constitutively secreted into the parasitophorous vacuole. Transgenic parasites in which the ROP5 antigenic epitope was targeted for secretion through dense granules led to enhanced CD8 T cell responses, whereas targeting the GRA6 epitope to rhoptries led to reduced CD8 responses. CD8 T cell responses to the dense-granule-targeted ROP5 epitope resulted in reduced parasite load in the brain. These data suggest that the mode of secretion affects the efficacy of parasite-specific CD8 T cell responses.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes / chemistry
  • Epitopes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / immunology*
  • Secretory Pathway*
  • Toxoplasma / immunology
  • Toxoplasma / metabolism*

Substances

  • Antigens, Protozoan
  • Epitopes
  • GRA6 protein, Toxoplasma gondii
  • Protozoan Proteins