Abstract

T cells expressing the TCR γδ constitute a small fraction of T cells in circulating blood whereas they are abundant in some peripheral lymphoid organs and mucosal sites. The TCR Vγ9/Vδ2 heterodimer is expressed on a large fraction of human TCR γδ cells. This receptor is activated by endogenous and bacterial phosphorylated metabolites, which accumulate in tumour transformed cells and in bacteria-infected cells. While the nature of the stimulatory ligands is known, it remains to be discovered how these novel antigens are handled within tumour and infected cells, how they are displayed on the surface of antigen presenting cells and whether a dedicated antigen-presenting molecule is involved. This review discusses the published data on the nature and structure of the human TCR γδ, the evidence of recognition of self and bacterial antigens, the events leading to accumulation of these metabolites and regulating their antigenicity. A hypothesis is presented on the possible mechanisms of antigen presentation to the TCR Vγ9/Vδ2 and the physiological role of TCR γδ cells in the immune response.