The cytoplasmic tail of the T cell receptor zeta chain is dispensable for antigen-mediated T cell activation.
The T cell antigen receptor consists of an antigen-binding alpha beta heterodimer and a group of invariant polypeptides denoted CD3-gamma, CD3-delta, CD3-epsilon and CD3-zeta. Whether antigen responsiveness is dependent on the expression of functional CD3-zeta subunit remains controversial. For instance, transfection of a zeta-/eta- variant of the 2B4.11. T cell hybridoma with mutated zeta cDNA that encoded a zeta protein truncated at residue 108, restored the surface expression of T cell antigen receptor complexes with, however, impaired antigen responsiveness [Frank, S. J., Niklinska, B. B., Orloff, D. G., Mercep, M., Ashwell, J. D. and Klausner, R. D., Science 1990. 249: 174.]. In marked contrast, BW5147 transfectants that expressed T cell antigen receptors devoid of functional zeta subunits were still able to trigger the production of interleukin-2 in response to antigen [Wegener, A.-M. K., Letourneur, F., Hoeveler, A., Brocker, T., Luton, F. and Malissen, B., Cell 1992. 68: 83.]. To assess if the above discrepancies may have resulted from the use of different recipient T cells, we transfected a zeta/eta-deficient variant of 2B4.11 (MA5.8) with the very same truncated zeta cDNA we previously used in BW5147. Consistent with our initial observations in BW5147, the cytoplasmic tail of the zeta polypeptide was found dispensable for antigenic responsiveness. Furthermore, a difference between the two recipient T cells was detected when cells were challenged via the Thy-1 and Ly-6 molecules. Once expressed in MA5.8, but not in BW5147, T cell antigen receptor complexes devoid of functional zeta subunits were able to sustain activation initiated via Thy-1 and Ly-6 molecules.
Hermans
M H
MH
Centre d'Immunologie, INSERM-CNRS de Marseille-Luminy, Marseille, France.
Malissen
B
B
D000818:Animals; D000941:Antigens / Q000276:immunology*; D000950:Antigens, Ly / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D018800:Thy-1 Antigens
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D018800:Thy-1 Antigens; C054979:antigen T cell receptor, zeta chain