IL-2-mediated T cell proliferation in humans is blocked by a monoclonal antibody directed against monomorphic determinants of HLA-DR antigens.

Abstract

We have studied the effect on the interleukin (IL-) 2-dependent human T cell growth of two distinct monoclonal antibodies (Mab), D1-12 and 4F2, with specificity for common determinant of human Ia antigens and for a differentiation antigen expressed on all activated T cells, respectively. Strong inhibition of cell growth was found in cultures supplemented with the anti-Ia D1-12 Mab but not in cultures supplemented with 4F2 Mab. These results were obtained when either total mixed leukocyte culture (MLC) T cells or an MLC-derived T cell clone were used as indicator cell systems for IL-2 activity. The inhibition of cell growth appears to be mediated by a direct interaction of D1-12 Mab with the cells and not by a direct inactivation of the growth factor, as addition of the antibody to murine MLC T cells, which do not express the determinant defined by D1-12 Mab, resulted in no inhibition of their proliferation induced by the same source of human IL-2.

Surface markers of resting and activated human T cells. Functional implications and experimental limits

“…Moreover IL-2 dependent growth of Ia + T cell clones is inhibited in a similar fashion by addition of anti-Ia antibodies [36]. Thus, it is conceivable that surface HLA-DR molecules may participate in the cellular events required for the transmission of the signal(s) given by IL-2 and resulting in cell proliferation [36]. Due to the recent discovery of different Ia loci, it is conceivable that by the use of mAbs directed against products of such different loci, different effects will be observed, possibly allowing the dissection of various components of the immune response.…”

“…In this connection, it has recently been shown that anti-Ia mAbs strongly inhibit the interleukin-2 (IL-2) dependent T cell proliferation. Moreover IL-2 dependent growth of Ia + T cell clones is inhibited in a similar fashion by addition of anti-Ia antibodies [36]. Thus, it is conceivable that surface HLA-DR molecules may participate in the cellular events required for the transmission of the signal(s) given by IL-2 and resulting in cell proliferation [36].…”

“…Thus, unlike resting T cells, Ia-positive activated T cells can function as effective stimulating populations both in allogeneic and in autologous MLC [33]; again, addition of anti-Ia mAbs completely inhibits cell proliferation. HLA-DR molecules present on activated T cells may also play a role in mechanisms regelating T cell division [36]. In this connection, it has recently been shown that anti-Ia mAbs strongly inhibit the interleukin-2 (IL-2) dependent T cell proliferation.…”

A New Monoclonal Antibody Recognizing a Linear Determinant on the HLA-DRα Chain N-terminus

“…(1)(2)(3)(4)(5) Monoclonal antibodies that specifically detect ''open'' or peptide-free MHC class II forms (4) offer insights into the peptide loading and related structural modifications involving HLA-DM. (5) Other monoclonal antibodies that react with the HLA class II abdimer have been utilized to identify epitopes critical for T cell recognition (5,6) and B cell activation. (7,8) In particular, the conformationally dependent MAbs L243 (9) and LB3.1 (10) have been exploited in many studies, identifying functionally important residues on HLA-DR ab-dimer.…”

HLA‐DR molecules enhance signal transduction through the CD3/Ti complex in activated T cells

“…A possible role for class I1 molecules in signal transduction in T cells was suggested by the findings that anti-class I1 mAb-inhibited proliferation of CD3-activated T cells and ILZdependent T-cell lines (7)(8)(9). Moreover, co-crosslinking DR enhanced CD3-induced IL2 production in T-leukemia cells (10).…”