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)

Effective stimulation of CD4+ T cells in an immune response depends on activation signals transduced via not only the CD3-T-cell receptor (TCR) complex but also those generated by accessory cell-surface proteins, including some that mediate adhesion between T cells and antigen-presenting cells (APC). Three members of the Ig superfamily, CD54 [intercellular cell adhesion molecule 1 (ICAM-1)], CD58 [lymphocyte function-associated antigen 3 (LFA-3)], and B7, expressed on the surface of APC, have been shown to mediate both adhesion and signaling during T cell-APC interactions. Recently another member of the Ig superfamily, [vascular cell adhesion molecule 1 (VCAM-1; INCAM110)], has been identified. VCAM-1 mediates adhesion between endothelial cells and activated lymphocytes and certain tumor cells. Here, using a soluble VCAM-1 fusion protein with receptor globulin (Rg), we examined the role of VCAM-1 in T-cell activation. We observed that CD4+ T cells, which are inefficiently stimulated by immobilized anti-TCR-1 or anti-CD3 monoclonal antibody (mAb) alone, can be induced to proliferate when exposed to immobilized VCAM-1-Rg in conjunction with either immobilized anti-TCR-1 or immobilized anti-CD3 mAb. The costimulatory effects of VCAM-1-Rg on CD4+T cells is inhibited by mAb to either the CD29 (integrin beta 1)-CD49d [very late activation antigen 4 alpha (VLA-4 alpha)] complex on the surface of CD4+ T cells or to VCAM-1. Stimulation of CD4+ T cells with immobilized VCAM-1-Rg and anti-TCR or -CD3 mAb results in the synthesis of both interleukin 2 (IL-2) receptors and IL-2. In addition, anti-CD25 (anti-IL-2 receptor a) mAb significantly inhibited the VCAM-1-Rg/anti-TCR or -CD3 mAb-driven activation of CD4+ T cells, indicating that endogenously produced IL-2 is in part responsible for the observed T-cell proliferation. Collectively, these results suggest that VCAM-1 can play an important costimulatory role during the activation of CD4+ T cells.
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PMID:Vascular cell adhesion molecule 1 induces T-cell antigen receptor-dependent activation of CD4+T lymphocytes. 171 78

Triggering of integrins can deliver signals that will regulate T cell activation and proliferation when coupled with TCR/CD3 signaling. While co-activation stimuli can be achieved either with immobilized natural ligands or immobilized monoclonal antibodies specific for various integrin subunits, counterposing effects can be delivered by ligation of the integrin beta 1 chain (CD29) resulting in the downregulation of T cell proliferation. Thus, integrins may play a pivotal role in cell activation and are involved in both positive and negative regulatory pathways. In this report, anti-beta 1 mAb 18D3 was used to investigate the role of beta 1 in the negative regulation of T cell proliferation. T lymphocytes were stimulated to proliferate when activated with immobilized mAb to CD3 in conjunction with all of a panel of immobilized mAb to different alpha 4 (CD49d) and beta 1 epitopes, except the anti-beta 1.1 mAb 18D3. In soluble form, mAb 18D3 inhibited the induction of DNA synthesis dependent on costimulation of CD3 and the integrin alpha 4 subunit by a mechanism independent of anti-adhesive properties. In kinetic experiments, the addition of mAb 18D3 effectively inhibited the ultimate induction of DNA synthesis at all time points until the time coinciding with the onset of T cell proliferation, indicating that triggering the beta 1.1 epitope may only act to quench activation events prior to cellular commitment to synthesize DNA. MAb 18D3 did not induce cell death nor render cells incompetent for restimulation, but appeared to selectively inhibit IL-2 synthesis with little effect on the induction of IL-2 receptor expression.
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PMID:MAb 18D3 triggering of integrin beta 1 will prevent but not terminate proliferation of human T cells. 752 62