Thomas R. Malek

Interleukin 2-driven T lymphocyte proliferation is dependent upon a surface antigen distinct from the interleukin 2 receptor: Requirements for inhibition of T-cell proliferation by monoclonal antibody 5C3

A monoclonal antibody (5C3) to an antigen expressed on activated guinea pig T lymphocytes that did not react with the interleukin 2 (IL-2) receptor, but inhibited IL-2-driven proliferative responses has been previously characterized. The present study provides further analysis of the inhibitory capacity of 5C3 for T-cell proliferation and of the relationship between the expression of the antigen defined by 5C3 and the capacity of cells to respond to IL-2. 5C3 inhibited proliferation of T-cell blasts to IL-2-containing fluids when added as late as 8 hr prior to termination of a 26-hr culture. 5C3 pretreatment of the IL-2-responsive blast cells was also sufficient to detect significant inhibition of proliferation. FACS analysis of these blasts indicated that maximal 5C3 binding was required for pretreatment to result in inhibition of IL-2-driven proliferation. Delayed addition of 5C3 to culture or pretreatment with 5C3 of responding cells also resulted in inhibition of proliferation of immune T lymphocytes to antigen-pulsed-presenting cells. Lastly, although modulated 5C3- blasts failed to proliferate to IL-2, induction of the 5C3-bearing molecule on these 5C3- blasts correlated with restoration of the ability of these cells to proliferate to IL-2. Collectively, these results further support the hypothesis that monoclonal antibody 5C3 interferes with a critical signal in the IL-2 growth pathway.

The Role of Macrophages in the Processing and Presentation of Protein Antigens to T Lymphocytes

It is clear that macrophages serve as antigen-presenting cells for a variety of specific immune responses and that many antigens are presented by macrophages to T lymphocytes in the context of the products of the I region of the major histocompatibility gene complex (MHC) of a species. For example, I-region-controlled genetic restrictions have been described for the development and expression of helper T cells (Erb and Feldmann, 1975a; Marrack and Kappler, 1978), for T-lymphocyte proliferation (Rosenthal and Shevach, 1976 Schwartz et al., 1978), and for delayed-type hypersensitivity (Miller, 1978). The use of recombinant and congenic mice and inbred guinea pigs has been an invaluable tool in establishing the role of the I region in antigen presentation. Furthermore, alloantisera to I-region gene products have demonstrated the necessity for the expression of Ia antigens on the surface of macrophages (Yamashita and Shevach, 1977; Cowing et al., 1978). The ability of multispecific anti-Ia sera to produce marked inhibition of in vitro antigen-specific T-lymphocyte proliferation to conventional and immune response (Ir) gene-controlled antigens (Shevach, 1978) indicated that a complex of Ia antigens and the nominal antigen was seen by the T lymphocyte.