T cell growth factor receptors. Quantitation, specificity, and biological relevance.
T cell growth factor receptors. Quantitation, specificity, and biological relevance.
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DOI：
10.1084/jem.154.5.1455
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发表时间：
1981-11-01
期刊：
影响因子：
--
通讯作者：
Smith KA
中科院分区：
文献类型：
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作者：
Robb RJ;Munck A;Smith KA
为了直接检验T细胞生长因子（TCGF）以类似于多肽激素的方式与靶细胞相互作用的假设，研究了放射性标记的TCGF与各种细胞群的结合。结果表明，TCGF通过一个受体与活化的T细胞相互作用，通过该受体启动T细胞增殖反应。内部放射性标记的TCGF由人T白血病细胞系制备，经凝胶过滤和等电聚焦纯化，保留了生物活性，大小和电荷均匀。放射性标记的TCGF与TCGF依赖性的细胞溶解性T细胞的结合发生迅速（在37摄氏度的15雨内），并且是饱和的，并且在很大程度上是可逆的。此外，在37℃时，TCGF发生了依赖受体和溶酶体的降解。放射性标记TCGF结合对活化的TCGF应答T细胞具有特异性。未受刺激的人或鼠淋巴细胞和脂多糖激活的B细胞母细胞表达很少（如果有）可检测的结合位点，而凝集素或同种异体抗原激活的细胞则容易检测到结合位点。此外，与凝集素或同种异体抗原激活的T细胞相比，长期依赖TCGF的细胞溶解和辅助T细胞系和TCGF依赖的新可塑性T细胞系以相似的亲和力结合TCGF（解离常数为5-25 pM），并且每个细胞表达相似数量的受体位点（5,000-15,000）。相比之下，许多T细胞、B细胞或骨髓来源的TCGF独立细胞系没有结合可检测到的放射性标记TCGF。放射性标记TCGF与TCGF应答细胞的结合具有特异性，因为在测试的几种生长因子和多肽激素中，只有TCGF竞争结合。最后，一定浓度的TCGF诱导的T细胞增殖的相对强度与占据受体位点的比例密切相关。由于T细胞克隆扩增的程度取决于TCGF和TCGF受体，这些研究允许的围绕TCGF及其受体相互作用的分子事件的解剖，应该为该淋巴因子对免疫反应的激素样调节提供新的见解。
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.