Eichmann K, Ehrfeld A, Falk I, Goebel H, Kupsch J, Reimann A, Zgaga-Griesz A, Saizawa K M, Yachelini P, Tomonari K
Max-Planck-Institut für Immunbiologie, Freiburg, Germany.
J Immunol. 1991 Oct 1;147(7):2075-81.
CD8 is a heterodimeric membrane glycoprotein on MHC class I-restricted T lymphocytes that cooperates with the alpha beta CD3 TCR in the recognition of MHC class I molecules presenting antigenic peptides. Co-operation has two components: enhancement of the affinity of MHC/peptide-TCR interaction, and signal transduction through the T cell membrane. The cytolytic function of CTL is primarily dependent on the affinity-enhancement component of CD8-TCR cooperation whereas activation of resting CD8+ T cells is primarily dependent on transmembrane signaling. Using a panel of mAb, two to the alpha-chain and three to the beta-chain of CD8, we investigated the relationships between epitopes and functional regions of the CD8 molecule. Two of the antibodies, one to the alpha-chain and one to the beta-chain of CD8, inhibit the cytolytic function of CTL but not the generation of CTL from resting T cells. Another two antibodies, also one to the alpha- and one to the beta-chain, inhibited the generation of CTL while enhancing the cytolytic function of CTL. These results suggest that both the alpha- and beta-chain of CD8 possess two distinct regions, one involved in affinity enhancement and the other in transmembrane signaling. The former may be the MHC class I-binding region whereas the latter may associate with the alpha beta CD3 TCR. The data can explain the apparent functional equivalence of CD8 alpha alpha homodimers and alpha beta heterodimers.
CD8是主要组织相容性复合体（MHC）I类限制性T淋巴细胞上的一种异二聚体膜糖蛋白，它与αβ CD3 T细胞受体（TCR）协同作用，识别呈递抗原肽的MHC I类分子。协同作用有两个组成部分：增强MHC/肽-TCR相互作用的亲和力，以及通过T细胞膜进行信号转导。细胞毒性T淋巴细胞（CTL）的细胞溶解功能主要依赖于CD8-TCR协同作用的亲和力增强成分，而静息CD8+ T细胞的激活主要依赖于跨膜信号传导。我们使用一组单克隆抗体（mAb），其中两种针对CD8的α链，三种针对β链，研究了CD8分子表位与功能区之间的关系。其中两种抗体，一种针对CD8的α链，一种针对β链，可抑制CTL的细胞溶解功能，但不影响静息T细胞产生CTL。另外两种抗体，同样一种针对α链，一种针对β链，可抑制CTL的产生，同时增强CTL的细胞溶解功能。这些结果表明，CD8的α链和β链都具有两个不同的区域，一个参与亲和力增强，另一个参与跨膜信号传导。前者可能是MHC I类结合区域，而后者可能与αβ CD3 TCR相关联。这些数据可以解释CD8αα同二聚体和αβ异二聚体明显的功能等效性。
