Szabó G, Weaver J L, Pine P S, Rao P E, Aszalos A
Department of Biophysics, University Medical School of Debrecen, Hungary.
Biophys J. 1995 Mar;68(3):1170-6. doi: 10.1016/S0006-3495(95)80293-6.
Instances when T cell activation via the T cell receptor/CD3 complex is suppressed by anti-CD4 Abs are generally attributed either to the topological separation of CD4-p56lck from CD3, or their improper apposition. Photobleaching fluorescence resonance energy transfer measurements permitted direct analysis of these alternatives on human peripheral blood lymphocytes. Distinction between changes of relative antigen densities or positioning was made possible by simultaneously recording donor and acceptor fluorescence in the energy transfer experiment performed on homogeneous populations of flow-sorted cells. We show here that CD4 stays in the molecular vicinity of CD3, while anti-CD3 stimulation is suppressed by anti-CD4 or cross-linked HIV gp120. Our data suggest that cross-linking of CD4 through particular epitopes is capable of inhibiting activation driven by Abs binding to specific sites on CD3 without major topological sequestration of the Ags, in such a way that additional positive signals will also be affected. Thus, these and other related cases of negative signaling via CD4 may be interpreted in terms of functional uncoupling rather than a wide physical separation of CD4 from the T cell receptor-CD3 complex.
通过T细胞受体/CD3复合物激活T细胞的过程被抗CD4抗体抑制的情况，通常归因于CD4-p56lck与CD3在拓扑结构上的分离，或者它们的不适当并列。光漂白荧光共振能量转移测量允许对人类外周血淋巴细胞上的这些可能性进行直接分析。通过在流式分选细胞的同质群体上进行的能量转移实验中同时记录供体和受体荧光，区分相对抗原密度或定位的变化成为可能。我们在此表明，CD4保持在CD3的分子附近，而抗CD3刺激被抗CD4或交联的HIV gp120抑制。我们的数据表明，通过特定表位交联CD4能够抑制由抗体结合CD3上的特定位点所驱动的激活，而不会使抗原发生主要的拓扑隔离，其方式是额外的阳性信号也会受到影响。因此，这些以及其他通过CD4进行负向信号传导的相关情况，可能应从功能解偶联的角度来解释，而不是CD4与T细胞受体 - CD3复合物在物理上的广泛分离。
