Activated CD8 binding to class I protein mediated by the T-cell receptor results in signalling.
The CD8 glycoprotein of T cells bind nonpolymorphic regions of class I major histocompatibility complex proteins on target cells and these interactions promote antigen recognition and signalling by the T-cell receptor. Studies using artificial membranes indicated that effective CD8/class I interaction is critical for response by alloantigen-specific cytotoxic T lymphocytes when class I protein is the only ligand on the antigen-bearing surface. But significant CD8-mediated binding of cytotoxic T lymphocytes to non-antigenic class I protein could not be detected in the absence of the alloantigen. These apparently contradictory findings indicate that CD8 binding to class I protein might be activated through the T-cell receptor and the results reported here demonstrate that this is the case. Treatment of cytotoxic T lymphocytes with soluble anti-T-cell receptor antibody activates adhesion of the cytotoxic T lymphocytes to class I, but not class II proteins. The specificity of this binding implies that it is mediated by CD8 and blocking by anti-CD8 antibodies confirmed this. Furthermore, binding of CD8 to class I protein resulted in generation of an additional signal(s) necessary to initiate response at low T-cell receptor occupancy levels.
O'Rourke
A M
AM
Division of Membrane Biology, Medical Biology Institute, La Jolla, California 92037.
Rogers
J
J
Mescher
M F
MF
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D016827:CD8 Antigens; D015550:Cell Degranulation; D002460:Cell Line; D006183:H-2 Antigens / Q000276:immunology*; D051379:Mice; D011485:Protein Binding; D047428:Protein Kinase Inhibitors; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D019311:Staurosporine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006183:H-2 Antigens; D047428:Protein Kinase Inhibitors; D011948:Receptors, Antigen, T-Cell; D019311:Staurosporine