The crystal structure of a TL/CD8alphaalpha complex at 2.1 A resolution: implications for modulation of T cell activation and memory

Immunity. 2003 Feb;18(2):205-15. doi: 10.1016/s1074-7613(03)00027-x.


TL is a nonclassical MHC class I molecule that modulates T cell activation through relatively high-affinity interaction with CD8alphaalpha. To investigate how the TL/CD8alphaalpha interaction influences TCR signaling, we characterized the structure of the TL/CD8alphaalpha 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/CD8alphaalpha interaction is strengthened through subtle structure changes in the TL alpha3 domain. Thus, TL functions to sequester and redirect CD8alphaalpha away from the TCR, modifying lck-dependent signaling.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD8 Antigens / chemistry*
  • CD8 Antigens / genetics
  • CD8 Antigens / metabolism
  • Crystallography, X-Ray
  • Immunologic Memory
  • Lymphocyte Activation
  • Macromolecular Substances
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Structure
  • Protein Binding
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • T-Lymphocytes / immunology*


  • CD8 Antigens
  • CD8 antigen, alpha chain
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Recombinant Proteins
  • thymus-leukemia antigens