The anti-CD6 mAb, IOR-T1, defined a new epitope on the human CD6 molecule that induces greater responsiveness in T cell receptor/CD3-mediated T cell proliferation.
The T lymphocyte cell surface molecule, CD6, has been shown in a number of studies to play an important role in T cell activation. Its physiological ligand or function is still unknown. A panel of five anti-CD6 mAbs was used in the present study to investigate the structure-function relationship of this molecule. Cross-blocking assays indicate that three different epitopes were defined on the CD6 molecule by these mAbs. One of these epitopes defined by the mAb, IOR-T1, is insensitive to thiol-reducing agents, such as dithiothreitol and 2-mercaptoethanol. Of the other two epitopes, one was defined by 2H1 and the other was shared by three other mAbs, T12, 6D3, and Dako-CD6. All the CD6 mAbs at optimal concentration exhibit equal potency in enhancing T cell proliferation mediated through the T cell receptor/CD3 complex by optimal concentration of the anti-CD3 mAb, OKT3 (100 ng/ml). Simultaneous cross-linking of both the anti-CD6 mAbs and OKT3 is essential for the synergistic effect. When suboptimal concentrations of OKT3 (1 ng/ml) were used (no detectable cell proliferation), the synergistic effect of the anti-CD6 mAbs was still evident but with a differential effect. The epitope defined by IOR-T1 consistently induced greater T cell responsiveness under these conditions. Our results suggest that the CD6 molecule may play an important role in T cell activation, and that signals through an epitope of stable conformation appear to be of importance when antigen levels are low or interacting with low-avidity antigen receptors.
Osorio
L M
LM
Departamento de Biologia, Instituto Nacional de Oncologia y Radiobiologia (INOR), La Habana, Cuba.
Garcia
C A
CA
Jondal
M
M
Chow
S C
SC
D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D001667:Binding, Competitive; D017252:CD3 Complex; D002460:Cell Line; D000939:Epitopes; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D011948:Receptors, Antigen, T-Cell; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; C062279:CD6 antigen; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell