| First Author | Mallaun M | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 12 | Pages | 8211-21 |
| PubMed ID | 18523287 | Mgi Jnum | J:137231 |
| Mgi Id | MGI:3798356 | Doi | 10.4049/jimmunol.180.12.8211 |
| Citation | Mallaun M, et al. (2008) The T cell receptor's alpha-chain connecting peptide motif promotes close approximation of the CD8 coreceptor allowing efficient signal initiation. J Immunol 180(12):8211-21 |
| abstractText | The CD8 coreceptor contributes to the recognition of peptide-MHC (pMHC) ligands by stabilizing the TCR-pMHC interaction and enabling efficient signaling initiation. It is unclear though, which structural elements of the TCR ensure a productive association of the coreceptor. The alpha-chain connecting peptide motif (alpha-CPM) is a highly conserved sequence of eight amino acids in the membrane proximal region of the TCR alpha-chain. TCRs lacking the alpha-CPM respond poorly to low-affinity pMHC ligands and are unable to induce positive thymic selection. In this study we show that CD8 participation in ligand binding is compromised in T lineage cells expressing mutant alpha-CPM TCRs, leading to a slight reduction in apparent affinity; however, this by itself does not explain the thymic selection defect. By fluorescence resonance energy transfer microscopy, we found that TCR-CD8 association was compromised for TCRs lacking the alpha-CPM. Although high-affinity (negative-selecting) pMHC ligands showed reduced TCR-CD8 interaction, low-affinity (positive-selecting) ligands completely failed to induce molecular approximation of the TCR and its coreceptor. Therefore, the alpha-CPM of a TCR is an important element in mediating CD8 approximation and signal initiation. |
