T Cell Activation by CD3 Antibodies

Abstract

Monoclonal antibodies which recognize the T3 antigen on human T cells have turned out to be excellent tools for analyzing T cell activation. The T3 antigen complex seems to be involved in specific immune functions, either as a receptor or as molecules functionally or physically associated with the receptor (1–3). In contrast to T cell activation by mitogens, the activation via anti-T3 antibodies seems to reflect antigen-specific lymphocyte stimulation. It is well established that mere binding of different anti-T3 antibodies triggers mitogenesis (4,5), induces the production of immune mediators like interferon (γ-IFN) and interleukin-2 (IL-2) (6–8), and blocks cytotoxic effector functions and antigen-specific proliferative responses (9). However, to date all studies of the activation of human T cells via the T3 antigen complex have been carried out with monoclonal antibodies of the IgG2a isotype (OKT3) or the IgG1 isotype (Leu-4, UCHT1). From the functional point of view the isotypes of anti-T3 antibodies seem to play a critical role in the efficiency and the mechanism of T cell activation. Whereas anti-T3 antibodies of the IgG2a isotype are highly effective in activating T cells from all donors by an IL2-dependent mechanism (8,10), for anti-T3 antibodies of IgG1 isotype nonresponsiveness caused by polymorphism in the accessory cell function has been described (11). Based on blocking experiments with Fc fragments of normal IgG (12,13) and analysis of different ethnic groups, the cause of nonresponsiveness seems to be genetic variations of the Fc-γ receptor of accessory cells (11,14).