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

Purified gammadelta 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 gammadelta 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 gammadelta T cells to MDP was analyzed by microarray, Q-PCR, proteome array and functional priming assays. MDP had a consistent priming effect on gammadelta T cells, characterized by changes in transcripts and enhanced proliferation response to secondary signaling. Knockdown experiments implicated Nod2 as the receptor for MDP in gammadelta T cell-enriched bovine PBLs. The results indicate priming of gammadelta T cells by MDP, and offer definitive evidence of the expression of functional Nod2 in gammadelta T cells.