The Crystal Structure of a TL/CD8αα Complex at 2.1 Å Resolution Implications for Modulation of T Cell Activation and Memory

AbstractTL is a nonclassical MHC class I molecule that modulates T cell activation through relatively high-affinity interaction with CD8αα. To investigate how the TL/CD8αα interaction influences TCR signaling, we characterized the structure of the TL/CD8αα complex using X-ray crystallography. Unlike antigen-presenting molecules, the TL antigen-binding groove is occluded by specific conformational changes. This feature eliminates antigen presentation, severely hampers direct TCR recognition, and prevents TL from participating in the TCR activation complex. At the same time, the TL/CD8αα interaction is strengthened through subtle structure changes in the TL α3 domain. Thus, TL functions to sequester and redirect CD8αα away from the TCR, modifying lck-dependent signaling