T cell growth factor receptors. Quantitation, specificity, and biological relevance

Abstract

To examine directly the hypothesis that T cell growth factor (TCGF) interacts with target cells in a fashion similar to polypeptide hormones, the binding of radiolabeled TCGF to various cell populations was investigated. The results indicate that TCGF interacts with activated T cells via a receptor through which it initiates the T cell proliferative response. Internally radiolabeled TCGF, prepared from a human T leukemia cell line and purified by gel filtration and isoelectric focusing, retained biological activity and was uniform with respect to size and charge. Binding of radiolabeled TCGF to TCGF-dependent cytolytic T cells occurred rapidly (within 15 rain at 37 degrees C) and was both saturable and largely reversible. In addition, at 37 degrees C, a receptor- and lysosome-dependent degradation of TCGF occurred. Radiolabeled TCGF binding was specific for activated, TCGF-responsive T cells. Whereas unstimulated lymphocytes of human or murine origin and lipopolysaccharide-activated B cell blasts expressed few if any detectable binding sites, lectin- or alloantigen-activated cells had easily detectable binding sites. Moreover, compared with lectin- or alloantigen-activated T cells, long-term TCGF-dependent cytolytic and helper T cell lines and TCGF-dependent neo-plastic T cell lines bound TCGF with a similar affinity (dissociation constant of 5-25 pM) and expressed a similar number of receptor sites per cell (5,000-15,000). In contrast, a number of TCGF-independent cell lines of T cell, B cell, or myeloid origin did not bind detectable quantities of radiolabeled TCGF. Binding of radiolabeled TCGF to TCGF-responsive cells was specific, in that among several growth factors and polypeptide hormones tested, only TCGF competed for binding. Finally, the relative magnitude of T cell proliferation induced by a given concentration of TCGF closely paralleled the fraction of occupied receptor sites. As the extent of T cell clonal expansion depends on TCGF and on the TCGF receptor, the dissection of the molecular events surrounding the interaction of TCGF and its receptor that these studies permit, should provide new insight into the hormonelike regulation of the immune response by this lymphokine.

Small-Molecule Inhibitors of IL-2/IL-2R: Lessons Learned and Applied

“…The IL-2 receptor family comprises three single-pass transmembrane proteins, IL-2Ra (p55, CD25), IL-2Rb (p75, CD122), and IL-2Rg (p64, CD132) (Robb et al 1981(Robb et al , 1984bLeonard et al 1984Leonard et al , 1985Greene et al 1986;Hatakeyama et al 1989;Tsudo et al 1990;Takeshita et al 1992;Noguchi et al 1993). IL-2Ra is present at low concentrations on T cells and is expressed along with IL-2 following TCR activation, forming a transient autocrine/paracrine signaling loop.…”

Ten‐Year Follow‐Up Study of Allergen‐Specific Immunoglobulin E and Immunoglobulin G4, Soluble Interleukin‐2 Receptor, Interleukin‐4, Soluble Intercellular Adhesion Molecule‐1 and Soluble Vascular Cell Adhesion Molecule‐1 in Serum of Patients on Immunotherapy for Perennial Allergic Rhinitis

“…Activation of T cells is associated with the expression of high-affinity IL-2 [27]. In serum IL-2R exists in soluble form (soluble IL-2R), and the rate of release of soluble IL-2R reflects T-cell activation in vivo [28].…”

Induction of granzyme B and T cell cytotoxic capacity by IL-2 or IL-15 without antigens: Multiclonal responses that are extremely lytic if triggered and short-lived after cytokine withdrawal

“…Both cytokines share a pair of receptor subunits, the gamma chain common to several cytokine receptors (γ c , CD132) combined with the IL-2/15 beta receptor chain (IL-2Rβ, CD122) [11]. Binding of either IL-2 or IL-15, with Kd's ~10 −9 M [12, 13,14], will activate this dimeric receptor to transmit intracellular signals via the JAK1/3-STAT3/5 pathways [15,16,17]. There are substantial numbers of these CD122/CD132 receptors on T cells and, at high concentrations (10 −8 M) of either IL-2 or IL-15, these receptors will be saturated.…”