Kuchroo V K, Byrne M C, Atsumi Y, Greenfield E, Connolly J B, Whitters M J, O'Hara R M, Collins M, Dorf M E
Department of Pathology, Harvard Medical School, Boston MA 02115.
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8700-4. doi: 10.1073/pnas.88.19.8700.
Antigen-specific suppressor T-cell hybridomas release soluble suppressor factors (TsF) in the supernatant that modulate both in vivo delayed-type hypersensitivity and in vitro plaque-forming cell responses in an antigen-specific manner. To study the relationship between the T-cell receptor (TcR) and TsF, we developed a series of TcR alpha- or TcR beta- expression variants from suppressor T-cell hybridomas that expressed the CD3-TcR alpha/beta complex. We demonstrate that loss of TcR alpha but not TcR beta mRNA was accompanied by the concomitant loss of suppressor bioactivity. Homologous transfection of TcR alpha cDNA into a TcR alpha- beta+ clone reconstituted both CD3-TcR expression and suppressor function. Furthermore, suppressor activity from TcR beta- variants was specifically absorbed by antigen and anti-TcR alpha antibodies, but not by anti-CD3 or anti-TcR beta affinity columns. These data directly establish a role for the TcR alpha chain in suppressor T-cell function and suggest that the TcR alpha chain is part of the antigen-specific TsF molecule.
抗原特异性抑制性T细胞杂交瘤在上清液中释放可溶性抑制因子(TsF),该因子以抗原特异性方式调节体内迟发型超敏反应和体外空斑形成细胞反应。为了研究T细胞受体(TcR)与TsF之间的关系,我们从表达CD3-TcRα/β复合物的抑制性T细胞杂交瘤中开发了一系列TcRα或TcRβ表达变体。我们证明,TcRα而非TcRβ mRNA的缺失伴随着抑制生物活性的同时丧失。将TcRα cDNA同源转染到TcRα-β+克隆中可重建CD3-TcR表达和抑制功能。此外,来自TcRβ变体的抑制活性被抗原和抗TcRα抗体特异性吸收,但不被抗CD3或抗TcRβ亲和柱吸收。这些数据直接确立了TcRα链在抑制性T细胞功能中的作用,并表明TcRα链是抗原特异性TsF分子的一部分。