The distinct response of γδ T cells to the Nod2 agonist muramyl dipeptide

Purified γδ T cells are primed directly in response to pathogen associated molecular patterns (PAMPs) to better respond to secondary signals and increase expression of chemokine and activation-related genes. Transcripts encoding the innate receptor Nod2 were detected in bovine and human γδ T cells. Nod2 is the intracellular receptor for muramyl dipeptide (MDP), functions in regulating innate activities, and was thought to be expressed primarily in APCs. The response of γδ T cells to MDP was analyzed by microarray, Q-PCR, proteome array and functional priming assays. MDP had a consistent priming effect on γδ T cells, characterized by changes in transcripts and enhanced proliferation response to secondary signaling. Knockdown experiments implicated Nod2 as the receptor for MDP in γδ T cell-enriched bovine PBLs. The results indicate priming of γδ T cells by MDP, and offer definitive evidence of the expression of functional Nod2 in γδ T cells.