A large collection of monoclonal antibodies (mAb) directed against sheep red blood cell (SRBC) receptor (cluster of differentiation 2: CD2) were classified according to three criteria: their inhibitory effect on T cell-SRBC rosette formation; the epitopic cluster recognized on the CD2 molecule; their reactivity with resting or activated T cells. All mAb were then tested in a two by two checkerboard fashion for possible T cell mitogenicity, in presence or absence of a submitogenic dose of 12-O-tetra-decanoylphorbol 13-acetate (TPA), an agent known to be comitogenic for T cells, presumably in delivering a second signal, usually accessory cell dependent. The combined data demonstrate that in the absence of TPA only few pairs of mAb directed at distinct epitopes of the CD2 molecule were mitogenic for T cells (in approximately 30% of the population tested), and in the presence of a submitogenic dose of TPA the majority of T11.1 anti-CD2-mAb (9 out of 11) were strongly mitogenic for T cells of all individuals tested when paired with T11.2 anti-CD2 mAb. The two anti-T11.1 mAb, noncomplementary to anti-T11.2 mAb, were, however, strongly mitogenic when added to mAb of the T11.3 subgroup, represented by 1-Mono-2A6. Taken together, these data strongly suggest that the main characteristic of T cell mitogenesis triggered by anti-CD2 mAb is the requirement for a signal delivered simultaneously to two different epitopes of the CD2 molecule, whether these epitopes are T11.1, T11.2 or T11.3.
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