Barbo J V, McCormack J E, Moorhead J W, Fairchild R L
Department of Immunology, Cleveland Clinic Foundation, OH 44195.
J Immunol. 1995 Feb 15;154(4):1551-9.
A population of CD8+ T cells from dinitrobenzene sulfonate-primed mice produce soluble effector molecules that down-regulate the magnitude of dinitrophenol-specific contact hypersensitivity reactions. These soluble molecules express the binding specificity and serologic determinants of alpha/beta TCR. To examine the requirement for the TCR-alpha chain in the production of these molecules, we have cloned the alpha-chain gene used to encode the surface TCR of MTs 79.1, a T cell hybridoma producing a DNP/Kd-specific soluble suppressive molecule, and tested the ability of this gene to reconstitute the production of the regulatory molecule in TCR alpha-chain gene deletion mutants. Transfection and expression of the alpha-chain construct into an alpha-chain deletion mutant of the parental hybridoma that expressed the parental beta-chain gene resulted in reconstitution of both surface TCR expression and production of the soluble suppressive molecule. As with the molecule produced by the MTs 79.1 parental cells, the inhibitory activity produced by these alpha-chain gene transfectants was DNP-specific and expressed determinants bound by anti-V beta 8 Abs. Transfection of the alpha-chain gene construct into an alpha-/beta- chain gene deletion mutant did not restore the production of the soluble regulatory molecule. These results indicate that in addition to the TCR beta-chain gene, expression of the TCR alpha-chain gene is also required for the production of these molecules. Our results strongly support the hypothesis that some forms of immunosuppression are mediated by soluble forms of the TCR.
来自二硝基苯磺酸盐致敏小鼠的一群CD8 + T细胞产生可溶性效应分子，这些分子可下调二硝基苯酚特异性接触性超敏反应的强度。这些可溶性分子表达α/β TCR的结合特异性和血清学决定簇。为了研究这些分子产生过程中对TCRα链的需求，我们克隆了用于编码MTs 79.1（一种产生DNP/Kd特异性可溶性抑制分子的T细胞杂交瘤）表面TCR的α链基因，并测试了该基因在TCRα链基因缺失突变体中重建调节分子产生的能力。将α链构建体转染并表达至表达亲本β链基因的亲本杂交瘤的α链缺失突变体中，导致表面TCR表达和可溶性抑制分子的产生均得以重建。与MTs 79.1亲本细胞产生的分子一样，这些α链基因转染子产生的抑制活性具有DNP特异性，并表达与抗Vβ8抗体结合的决定簇。将α链基因构建体转染至α/β链基因缺失突变体中并不能恢复可溶性调节分子的产生。这些结果表明，除了TCRβ链基因外，这些分子的产生还需要TCRα链基因的表达。我们的结果有力地支持了某些形式的免疫抑制是由TCR的可溶性形式介导的这一假说。
