Van Seventer G A, Van Lier R A, Spits H, Ivanyi P, Melief C J
Eur J Immunol. 1986 Nov;16(11):1363-71. doi: 10.1002/eji.1830161109.
The functional role of the T8 antigen of human T cells was studied by inhibition with anti-T8 monoclonal antibodies (mAb) of the cytotoxic action of T8+ cytotoxic T lymphocyte clones (CTL). All clones were allospecific and directed against HLA-B7. The ability of seven different anti-T8 mAb to inhibit the cytotoxicity of these alloreactive CTL clones corresponded with their avidity for a particular target cell. The lysis of cross-reactive antigen-bearing target cells was more readily blocked by anti-T8 mAb than lysis of the specific B7 target cell against which a clone was raised. The seven anti-T8 mAb showed a spectrum of CTL blocking ability ranging from strong blocking with all five CTL clones tested to weak inhibition of only two out of five clones. mAb inhibition of CTL reactivity and cold target inhibition studies with one of the five CTL clones indicate a post-binding role of the T8 molecule. Functional epitope mapping based on CTL blocking with the anti-T8 mAb resulted in the definition of one nonfunctional epitope on the T8 molecule which is only expressed on mature T lymphocytes and a cluster of closely related functional epitopes expressed on both thymocytes and mature T lymphocytes. Not only allospecific cytotoxicity, but also nonspecific cytotoxicity induced anti-T3 mAb in these allospecific clones was inhibited by anti-T8 mAb in the absence of HLA class I expression on the target cell (Daudi cell line). The hierarchy of blocking with anti-T8 mAb and the classification of functional epitopes on T8 in anti-T3-induced nonspecific cytotoxicity were similar to those obtained in blocking of allospecific reactivity of the CTL clones. This analogy points to an identical function of the T8 antigen in both allospecific and anti-T3-induced nonspecific cytotoxicity. If HLA class I molecules are the counter structures of the T8 antigen, then these results argue against an adhesion-like function of the T8 structure. The combined results show that the T8 molecule has a regulatory role in CTL activation. It is postulated that the T8 antigen might serve as a receptor that transduces a negative feedback signal for T cell activation which prevents T cell triggering by nonspecific interaction.
通过用抗T8单克隆抗体（mAb）抑制T8 + 细胞毒性T淋巴细胞克隆（CTL）的细胞毒性作用，研究了人T细胞T8抗原的功能作用。所有克隆均为同种异体特异性，且针对HLA - B7。七种不同的抗T8 mAb抑制这些同种异体反应性CTL克隆细胞毒性的能力与其对特定靶细胞的亲和力相对应。与针对克隆所针对的特异性B7靶细胞的裂解相比，抗T8 mAb更容易阻断携带交叉反应性抗原的靶细胞的裂解。七种抗T8 mAb表现出一系列的CTL阻断能力，从对所有五个测试的CTL克隆都有强烈阻断作用到仅对五个克隆中的两个有弱抑制作用。mAb对CTL反应性的抑制以及对五个CTL克隆之一进行的冷靶抑制研究表明T8分子在结合后起作用。基于用抗T8 mAb阻断CTL的功能表位图谱分析，确定了T8分子上一个仅在成熟T淋巴细胞上表达的无功能表位，以及在胸腺细胞和成熟T淋巴细胞上均表达的一组紧密相关的功能表位。在靶细胞（Daudi细胞系）上不存在HLA I类表达的情况下，抗T8 mAb不仅抑制了这些同种异体特异性克隆中的同种异体特异性细胞毒性，还抑制了抗T3 mAb诱导的非特异性细胞毒性。抗T8 mAb的阻断层次以及T8在抗T3诱导的非特异性细胞毒性中的功能表位分类与在阻断CTL克隆的同种异体特异性反应性中获得的结果相似。这种相似性表明T8抗原在同种异体特异性和抗T3诱导的非特异性细胞毒性中具有相同的功能。如果HLA I类分子是T8抗原的对应结构，那么这些结果与T8结构的粘附样功能相悖。综合结果表明，T8分子在CTL激活中具有调节作用。据推测，T8抗原可能作为一种受体，转导T细胞激活的负反馈信号，从而防止T细胞通过非特异性相互作用被触发。
