NOVAGAMD · Novel antigens for human gamma delta T cells

T lymphocytes bearing gamma delta T cell receptors (TCR) make crucial contributions to tissue-surveillance of infection and non-microbial stress. Although these cells may recognise dysregulated tissues via their activating NKG2D receptor, we remain very ignorant of stress-related molecules that may bind the gamma/delta TCR directly. Much work has focussed on peripheral blood gamma delta T cells expressing Vgamma9-Vdelta2 TCRs. Recently however, several Vgamma9-Vdelta2-negative clones were isolated which react both to cytomegalovirus-infected cells and to colonic tumours. This has led to the identification of Endothelial cell Protein C Receptor (EPCR) as a TCR target of one such clone. This is only the third gamma delta TCR ligand validated biochemically. I shall now assess the generality of EPCR reactivity among human gamma delta T cells. Using ELISpot technology, I can apply a very sensitive means to investigate cytokine production by gamma delta T cells from cells of donors of various ages and health status. Moreover, since EPCR is strongly conserved, I shall extend the project to mouse. The identification of EPCR activity in mice would substantially enhance the capacity to dissect the biology of this novel response. Finally, I shall also investigate candidate ligands for aVgamma9-Vdelta2-negative clone that does not bind EPCR.