Pecht I, Corcia A, Liuzzi M P, Alcover A, Reinherz E L
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
EMBO J. 1987 Jul;6(7):1935-9. doi: 10.1002/j.1460-2075.1987.tb02454.x.
T lymphocytes are activated to proliferate via a surface membrane receptor recognizing the antigen/major histocompatibility complex. This membrane component is comprised of at least five polypeptide subunits, collectively termed the Ti-T3 receptor complex. A transient increase in cytosolic free calcium occurs as an early event in the T-cell activation process and is necessary for induction of the endogenous IL-2 and certain other genes. Monoclonal antibodies specific to epitopes of either the Ti or the T3 components were shown to be effective agonists, also leading to such transient rises in cytosolic free calcium and activating the lymphocytes. Here we show, using micropipette-supported bilayers formed from membranes of the human T-cell line REX, that Ti- or T3-specific antibodies cause opening of ligand gated ion channels. Both types of specific antibodies yielded similar histograms of conductance amplitudes which show a channel with a conductance of 2-3 pS in symmetrical 100 mM CaCl2 solutions. These channels allow the passage of calcium and barium ions and are blocked by lanthanum ions, suggesting that they are specific for calcium. We propose that these channels, by allowing the entry of external calcium, may account for a large fraction of the rise in intracellular calcium observed upon triggering of the Ti-T3 receptor.
T淋巴细胞通过识别抗原/主要组织相容性复合体的表面膜受体被激活而增殖。这种膜成分由至少五个多肽亚基组成，统称为Ti-T3受体复合体。胞质游离钙的短暂增加是T细胞激活过程中的早期事件，对于内源性白细胞介素-2和某些其他基因的诱导是必需的。已证明对Ti或T3成分表位特异的单克隆抗体是有效的激动剂，也会导致胞质游离钙的这种短暂升高并激活淋巴细胞。在此我们使用由人T细胞系REX的膜形成的微吸管支持的双层膜表明，Ti或T3特异性抗体导致配体门控离子通道开放。两种类型的特异性抗体产生了相似的电导幅度直方图，在对称的100 mM氯化钙溶液中显示出一个电导为2-3 pS的通道。这些通道允许钙和钡离子通过，并被镧离子阻断，表明它们对钙具有特异性。我们提出，这些通道通过允许外部钙进入，可能是触发Ti-T3受体后观察到的细胞内钙升高的很大一部分原因。
