On the role of CD3delta chains in TCRgammadelta/CD3 complexes during assembly and membrane expression.

Abstract

The present study was performed in order to analyze whether T-cell receptor (TCR)/CD3 assembly, intracellular transport and surface expression are carried in a similar way in alphabeta-and gammadelta-T cells. By means of optimal immunoprecipitation conditions with 35S-methionine/cysteine- or biotin-labelled TCR/CD3 proteins from alphabeta- or gammadelta-T-lymphoma-cell lines, as well as TCRgammadelta cDNA transfectants, it was found that CD3delta chains associate less strongly with TCRgammadelta heterodimers compared to TCRalphabeta heterodimers. This preferential reactivity of CD3delta chains appears to be structural and not owing to differences in gammadelta- versus alphabeta-T-cell intracellular environments. Our results are in accordance firstly, with data from CD3delta-deficient mice, which have gammadelta-T cells but no alphabeta-T cells, secondly with the suggested role of CD3delta chains in the positive selection of alphabeta-T cells, a process apparently not followed by gammadelta-T cells, and lastly with the differential roles of CD3delta chains versus CD3gamma chains, explaining the maintenance of two CD3delta and CD3gamma genes after the duplication from a CD3delta/gamma gene present in avians. The impaired reactivity of CD3delta chains with TCRgammadelta heterodimers seems to be owing to a less efficient association with TCRgamma chains. In contrast, CD3delta chains interact as strongly with TCRdelta chains as do CD3gamma chains with both TCRgamma and TCRdelta chains. These data may explain, at the molecular levels, why surface TCR/CD3 expression levels are impaired in gammadelta-T cells from CD3gamma-deficient mice but not from CD3delta-deficient mice.