RECOGNITION BY γ/δ T CELLS

Abstract

▪ Abstract In contrast with the study of αβ T cells, that of γδ T cells is relatively recent and stems from the discovery of their rearranged genes, rather than from any knowledge of their biological function. Thus, experiments designed to characterize their specificity and function have drawn heavily on our knowledge of αβ T cells. During the past few years, many studies, especially with mice lacking either αβ or γδ T cells, have demonstrated that γδ T cells can contribute to immune competence, but they do so in a way that is distinct from αβ T cells. It is also evident that γδ T cells may not recognize antigen the same way as do αβ T cells. Analysis of three protein antigens—the murine MHC class II IE^k, the nonclassical MHC T10/T22, and the Herpes virus glycoprotein gI—indicates that γδ T cell recognition does not require antigen processing and that the proteins are recognized directly. In all three cases, recognition by these T cell clones involves neither peptides bound to these proteins nor peptides derived from them. Moreover, a group of small phosphate-containing nonpeptide compounds derived from mycobacterial extracts has been found to stimulate a major population of human peripheral γδ T cells in a T cell receptor (TCR)-dependent manner. This indicates that γδ T cells can respond to ligands that are different from those of α β T cells.Analysis of complementarity determining region (CDR3) length distributions of γ and δ chains indicates that they are more similar to those of immunoglobulins than to TCR α and β. This further supports the idea that γδ and αβ T cells recognize antigens differently and suggests that γδ T cells may be more like immunoglobulins in their recognition properties. γδ T cells share many cell surface proteins with αβ T cells and are able to secrete lymphokines and express cytolytic activities in response to antigenic stimulation. These, together with the results cited above, indicate that γδ T cells can mediate cellular immune functions without a requirement for antigen processing. Thus, pathogens, damaged tissues, or even B and T cells can be recognized directly, and cellular immune responses can be initiated without a requirement for antigen degradation or specialized antigen-presenting cells. This would give γδ T cells greater flexibility than the more classical type of αβ T cell–mediated cellular immunity.