The CD8 beta polypeptide is required for the recognition of an altered peptide ligand as an agonist.
T cell activation is triggered by the specific recognition of cognate peptides presented by MHC molecules. Altered peptide ligands are analogs of cognate peptides which have a high affinity for MHC molecules. Some of them induce complete T cell responses, i.e. they act as agonists, whereas others behave as partial agonists or even as antagonists. Here, we analyzed both early (intracellular Ca2+ mobilization), and late (interleukin-2 production) signal transduction events induced by a cognate peptide or a corresponding altered peptide ligand using T cell hybridomas expressing or not the CD8 alpha and beta chains. With a video imaging system, we showed that the intracellular Ca2+ response to an altered peptide ligand induces the appearance of a characteristic sustained intracellular Ca2+ concentration gradient which can be detected shortly after T cell interaction with antigen-presenting cells. We also provide evidence that the same altered peptide ligand can be seen either as an agonist or a partial agonist, depending on the presence of CD8beta in the CD8 co-receptor dimers expressed at the T cell surface.
Renard
V
V
Centre d'Immunologie INSERM/CNRS de Marseille-Luminy, France.
Delon
J
J
Luescher
I F
IF
Malissen
B
B
Vivier
E
E
Trautmann
A
A
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects*; D016827:CD8 Antigens / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D007376:Interleukin-2 / Q000096:biosynthesis; D007739:L Cells; D008024:Ligands; D051379:Mice; D010455:Peptides / Q000819:agonists* / Q000276:immunology* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
D016827:CD8 Antigens; D007376:Interleukin-2; D008024:Ligands; D010455:Peptides; D002118:Calcium