Mechanisms determining cell membrane expression of different gammadelta TCR chain pairings

We investigated the ability of the most common TCR-gamma and delta chains to express on the cell surface. Vgamma1Cgamma4 and Vgamma7Cgamma1 chains paired with all TCR-delta chains tested, whereas Vgamma4Cgamma1 chains were found with Vdelta4 and Vdelta5, but not with Vdelta2 or Vdelta6 chains, and Vgamma2Cgamma2 chains were expressed only with Vdelta5. Mapping studies showed that up to four polymorphic residues influence the different co-expressions of Vgamma1 and Vgamma2 chains with Vdelta chains. Unexpectedly, these residues are not located in the canonical gamma/delta interface, but in the outer part of the gammadelta TCR complex exposed to the solvent. Expression of functional Vdelta4 or Vdelta6 chains in Vgamma2/Vdelta5(+) cells or of functional Vgamma2Cgamma2 in Vgamma1(+) cells reduced cell-surface expression of the gammadelta TCR. Taken together, these data show that (i) the Vgamma/Vdelta repertoire of mouse gammadelta T cells is reduced by physical constraints in their associations. (ii) Lack of Vgamma2/Vdelta expression is due to the formation of aberrant TCR complexes, rather than to an intrinsic inability of the chains to pair and (iii) despite not being expressed at the cell surface, the presence of a functionally rearranged Vgamma2 chain in gammadelta T cells results in reduced TCR levels.