Specificity and selection of gamma-delta receptor-expressing T cells.

Abstract

It is not yet possible to establish a unifying hypothesis regarding TCR-γσ selection, specificity, and function. TCR-γσ-bearing T cells have been characterized that are specific for classical MHC and nonclassical MHC-like antigens, and mycobacterial antigens, including bacterial and possibly self heat-shock proteins. Restricting elements for these antigen-specific TCR-γσ T cells are still obscure, and it is unknown whether they are positively selected during development. However, there is now definitive evidence for intrathymic negative selection of TCR-γσ, and intriguing data suggesting positive selection of certain TCR-γσ that takes place in the periphery and is mediated by non MHC-linked antigens. The central question remains, what critical and unique role, if any, do these T cells play in immune system function? Proposals such as TCR-γσ functioning as an epithelial surveillance system (perhaps not relevant to human TCR-γσ), or as a first line of response to certain bacterial infections, and even a role for TCR-γσ in early intrathymic T cell differentiation all retain validity, and provide testable model systems for further study.