Diversity of γδ T-cell antigens

Abstract

In the last two decades, it has become clear that γδ T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, γδ antigens as a whole resemble more the antigens recognized by antibodies than those recognized by αβ T cells. Because of this antigenic diversity, no single mechanism-such as the major histocompatibility complex (MHC) restriction of αβ T cells-is likely to provide a basis for all observed T-cell antigen receptor (TCR)-dependent γδ T-cell responses. Furthermore, available evidence suggests that many individual γδ T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of γδ T-cell populations, and thus generate a more efficient immune response.

Figure 1

γδ T cells recognize a wide range of structurally different ligands. Unlike most αβ T cells, γδ T cells recognize ligands that vary much in size, composition and molecular structure, including MHC and non-MHC cell surface molecules, soluble proteins and smaller peptides, phospholipids, prenyl pyrophosphates and sulfatide. Some of these molecules appear to be recognized in complex with others (e.g. certain phospholipids in complex with CD1d or apo H), and most if not all are recognized while bound to or expressed on the cell surface. apo H, apolipoprotein H; MHC, major histocompatibility complex.