Specific inhibition of OKT3-driven T-cell mitogenesis by an anti HLA-class I monoclonal antibody.
Triggering of the T-cell receptor by anti-CD3 monoclonal antibodies (mAb), for example OKT3, induces accessory cell (AC)-dependent interleukin-2 (IL-2) and IL-2 receptor synthesis, and ultimately, T-cell proliferation. We report on the ability of a HLA-class I specific monomorphic mAb, namely FMC16, to inhibit OKT3-driven T-cell mitogenesis. FMC16 was apparently selective for OKT3 because it did not block Concanavalin A (Con A) or mAb Leu-4 induced proliferation. Moreover, this effect was not due to non-specific toxicity nor interference with OKT3 binding. Kinetic analysis showed that FMC16 was inhibitory when added up to 24 hr after initiation of culture. FMC16 drastically reduced both IL-2 production and IL-2 receptor expression, but did not interfere with IL-2 responsiveness. The inhibitory effects were not altered by the addition of exogenous IL-2 if FMC16 was present at the beginning of culture; however, IL-2 did restore proliferation if FMC16 was not added until 3 to 6 hr after initiation of culture. This coincided exactly with an IL-2 mediated increase in the level of TAC-positive cells. Furthermore, T-cell activation triggered by the synergistic action of OKT3 and a phorbol ester (TPA) in the absence of AC was also blocked by FMC16, suggesting that inhibition was not AC-dependent. Taken together, these results indicate that FMC16 interferes with early signals leading to IL-2 production and IL-2 receptor expression and suggest that HLA-class I determinants play an early role in T-cell activation.
Beckman
I
I
Department of Clinical Immunology, Flinders Medical Centre and University, Bedford Park, Adelaide, South Australia.
Xiaoning
X
X
Bradley
J
J
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D002478:Cells, Cultured; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006680:HLA Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2