Differentiation of Human T Cells Alters Their Repertoire of G Protein α-Subunits

Because T cell differentiation leads to an expanded repertoire of chemokine receptors, a subgroup of G protein-coupled receptors, we hypothesized that the repertoire of G proteins might be altered in parallel. We analyzed the abundance of mRNA and/or protein of six G protein α-subunits in human CD4+ and CD8+ T cell subsets from blood. Although most G protein α-subunits were similarly expressed in all subsets, the abundance of Gαo, a protein not previously described in hematopoietic cells, was much higher in memory versus naive cells. Consistent with these data, activation of naive CD4+ T cells in vitro significantly increased the abundance of Gαo in cells stimulated under nonpolarizing or TH17 (but not TH1 or TH2)-polarizing conditions. In functional studies, the use of a chimeric G protein α-subunit, Gαqo5, demonstrated that chemokine receptors could couple to Gαo-containing G proteins. We also found that Gαi1, another α-subunit not described previously in leukocytes, was expressed in naive T cells but virtually absent from memory subsets. Corresponding to their patterns of expression, siRNA-mediated knockdown of Gαo in memory (but not naive) and Gαi1 in naive (but not memory) CD4+ T cells inhibited chemokine-dependent migration. Moreover, although even in Gαo- and Gαi1-expressing cells mRNAs of these α-subunits were much less abundant than Gαi2 or Gαi3, knockdown of any of these subunits impaired chemokine receptor-mediated migration similarly. Together, our data reveal a change in the repertoire of Gαi/o subunits during T cell differentiation and suggest functional equivalence among Gαi/o subunits irrespective of their relative abundance.