Changes in Arrangement and in Conformation of Molecular Components of Peripheral T‐Cell Antigen Receptor Complex After Ligand Binding: Analyses by Co‐Precipitation Profiles

Abstract

Amounts of co-precipitating CD3 components by anti-T-cell receptor (TCR)Vb or anti-CD4/8 monoclonal antibodies were compared between non-stimulated and stimulated splenic T cells. The amounts of co-precipitating CD3d, e and g chains with TCRab and with CD4/8 were not significantly changed after TCR ligation. The apparent amount of CD3z chain co-precipitated with TCRab increased up to threefold, while the actual amount of co-precipitating CD3z with TCRab and the total amount of specifically precipitated CD3z are not changed after cross linking of TCR. The apparent amount of CD3z chain co-precipitated with CD4/8 also increased. Unlike co-precipitation with TCRab, the actual amount of CD3z co-precipitated with CD4/8 increased significantly. This observation suggests a conformational change as well as the relocation of CD3z molecules within the TCR complex after the signal delivery. After TCR ligation, CD3z chains relocate to the vicinity of either CD4 or CD8 molecules. In addition, when cross linking and binding signals are compared, CD3 chains undergo two distinct phases of conformational change. The early conformational change caused by ligand binding is positively related to the induction of proliferative responses, while the later conformational change caused by the cross linking of TCR does not induce but enhances the proliferative response.

The short length of the extracellular domain of ζ is crucial for T cell antigen receptor function

“…Surface-biotinylation and epitope-accessibility data provided further support to this hypothesis [8,9]. Interestingly, after prolonged stimulation with antigen-presenting cells, exposure of the EC part was detected, indicating that stimulation of the TCR induces architectural changes in the complex [7][8][9]. The TCR␣␤ heterodimer cannot directly communicate with cytoplasmic signalling proteins.…”

“…The short length of the EC domain (nine amino acids) supports this possibility. Further support for this hypothesis comes from surface-biotinylation and epitope-accessibility data [8,9]. Since the primary amino acid sequence of the EC part is highly conserved among mammals ( Fig.…”

Interaction between the CD8 Coreceptor and Major Histocompatibility Complex Class I Stabilizes T Cell Receptor-Antigen Complexes at the Cell Surface

“…However, structural and biophysical studies of soluble TCR and CD8 do not rule out the possibility that CD8 on the CTL surface enhances TCR binding to pMHCI on the antigen-presenting cell surface. Mounting evidence shows that CD8 can interact directly with the TCR (17,(23)(24)(25)(26)(27)(28)(29) and appears to have an important role in organizing the TCR on the T cell surface (13,30). Direct TCR/ CD8 association on the CTL surface could therefore enable cooperativity in pMHCI binding that would not be detectable using soluble versions of these molecules.…”

Monomeric Class I Molecules Mediate TCR/CD3ε/CD8 Interaction on the Surface of T Cells

“…However, there are conflicting reports regarding which interactions between the coreceptors and TCR/CD3 are affected during T cell activation. Osono et al (11) reported that upon activation with anti-TCR␤ Abs, interactions between CD3␥-, ␦-, and ⑀-chains and coreceptor molecules remain unchanged, whereas CD3-CD4/8 association is augmented during activation. In contrast to this, Anel et al (12) showed enhanced CD3⑀-CD8 association upon Con A activation.…”