Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that monoclonal antibodies (mAbs) against certain gangliosides, which induced remissions in patients with melanoma, also potentiated the response of lymphocytes to a variety of stimuli, including lectins, interleukin-2 (IL-2) and antigens. The present studies have investigated the mechanism of these effects on lymphocytes. Although the mAbs potentiated phytohemagglutinin(PHA)-induced IL-2 production at high concentrations of mAbs and of PHA, this did not appear to explain their potentiation of the proliferative responses of lymphocytes. Hence, although IL-2 production was minimal or absent from the CD8+ subset the latter showed the highest degree of augmentation. Furthermore, addition of IL-2 to PHA-stimulated cultures did not produce similar augmentation of mitogenic responses to that produced by the mAb to GD3 or GD2. The augmented and normal mitogenic responses were, however, dependent on IL-2, as shown by their inhibition with mAbs against IL-2. The antiganglioside mAbs did not have significant effects on IL-2 receptor expression measured by mAbs to Tac. However, the mAbs appeared to increase the affinity of binding of radiolabelled IL-2 to IL-2 receptor and increased internalization of the latter. These results suggest that the effects of the mAbs on IL-2 production may be distinguished from their effects on the proliferative responses of T cells and that the latter were associated with changes in affinity and internalization of 125I-IL-2. Whether the latter is a direct cause of the increased proliferative response remains unknown. The ability of mAbs to GD2 and GD3 to increase IL-2 production and to "enhance" IL-2-dependent proliferative responses suggests the may have valuable clinical roles as immunopotentiating agents.
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PMID:Potentiation of interleukin-2 production and its binding by monoclonal antibodies to the gangliosides GD3 and GD2. 252 55

The ganglioside GD3 has been described as a membrane component of human T cells which is involved in T cell growth. In the present study the activating function of GD3 for human CD4+ and CD8+ T cells was analyzed by five different monoclonal antibodies (mAb) directed against the GD3 molecule. Three mAb U5, Z21 and R24 induced strong proliferation of peripheral blood mononuclear cells and purified CD8+ and CD4+ T cells of normal donors containing less than 5% CD16+ natural killer (NK) cells. In contrast to CD4+ T cells, CD8+ T cells proliferated only weakly in the presence of 15% CD16+ NK cells. The proliferative response of purified CD4+ and CD8+ T cells (< 5% NK cells) correlated with the antibody-dependent induction of integral and soluble interleukin-2 (IL-2) receptors and was reduced to 20% by an anti-IL-2 receptor antibody. Our results show, that the GD3 molecule represents an activation molecule for both CD4+ and CD8+ T cells and that CD16+ NK cells selectively inhibit anti-GD3 antibody-induced proliferation of CD8+ T cells.
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PMID:Inhibition of anti-GD3-ganglioside antibody-induced proliferation of human CD8+ T cells by CD16+ natural killer cells. 818 30

R24 is a monoclonal antibody directed against the cell surface ganglioside GD3. It can detect GD3 on the surface of a subset of T lymphocytes and can stimulate proliferation and secretion of cytokines in vitro. In the present report, we examined the effects of the R24 antibody upon antigen-specific T cell response, employing an HLA-DR7-specific T cell clonal model. As previously shown, primary stimulation of HLA-DR7-specific alloreactive T cell clones by transfectants expressing HLA-DR7 alone (t-DR7) in the absence of B7 co-stimulation resulted in anergy. Binding of cell surface GD3 on HLA-DR7-specific alloreactive T cell clones with R24 under these anergizing conditions resulted in interleukin-2 (IL-2) accumulation and prevented the induction of alloantigen-specific T cell clonal anergy. Binding of GD3 by R24 also prevented anergy under conditions where B7:CD28 interactions were blocked by CTLA4-Ig. The effect of R24 was abrogated in the presence of a combination of monoclonal antibodies for the alpha and beta chains of the IL-2 receptor (IL-2R) or a neutralizing anti-IL-2 antibody. R24 does not appear to interact directly with the IL-2R since incubation of T cell clones with R24 did not induce early activation of IL-2R associated Jak kinases, Jak1 and Jak3, as was induced following incubation with IL-2. In contrast, incubation of HLA-DR7-specific clones with t-DR7 in the presence of R24 did result in phosphorylation of IL-2R related Jak kinases after 24 h. Our data indicate that the membrane ganglioside GD3 structure recognized by R24 may play an important role in antigen-specific T cell clonal response.
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PMID:R24 anti-GD3 ganglioside antibody can induce costimulation and prevent the induction of alloantigen-specific T cell clonal anergy. 881 60