RECOGNITION BY GAMMA DELTA T-CELLS

In contrast with the study of alpha beta T cells, that of gamma delta T cells is relatively recent and stems from the discovery of their rea rranged genes, rather than from any knowledge of their biological func tion. Thus, experiments designed to characterize their specificity and function have drawn heavily on our knowledge of alpha beta T cells. D uring the past few years, many studies, especially with mice lacking e ither alpha beta or gamma delta T cells, have demonstrated that gamma delta T cells can contribute to immune competence, but they do so in a way that is distinct from alpha beta T cells. It is also evident that gamma delta T cells may not recognize antigen the same way as do alph a beta T cells. Analysis of three protein antigens-the murine MHC clas s II IE(k), the nonclassical MHC T10/T22, and the Herpes virus glycopr otein gI-indicates that gamma delta T cell recognition does not requir e 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. Moreo ver, a group of small phosphate-containing nonpeptide compounds derive d from mycobacterial extracts has been found to stimulate a major popu lation of human peripheral gamma delta T cells in a T cell receptor (T CR)-dependent manner. This indicates that gamma delta T cells can resp ond to ligands that are different from those of alpha beta T cells. An alysis of complementarity determining region (CDR3) length distributio ns of gamma and delta chains indicates that they are more similar to t hose of immunoglobulins than to TCR alpha and beta. This further suppo rts the idea that gamma delta and alpha beta T cells recognize antigen s differently and suggests that gamma delta T cells may be more like i mmunoglobulins in their recognition properties. gamma delta T cells sh are many cell surface proteins with alpha beta T cells and are able to secrete lymphokines and express cytolytic activities in response to a ntigenic stimulation. These, together with the results cited above, in dicate that gamma delta 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 cellul ar immune responses can be initiated without a requirement for antigen degradation or specialized antigen-presenting cells. This would give gamma delta T cells greater flexibility than the more classical type o f alpha beta T cell-mediated cellular immunity.