The crystal structure of a TL/CD8alphaalpha complex at 2.1 A resolution: implications for modulation of T cell activation and memory.
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.
Liu
Yiwei
Y
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Xiong
Yi
Y
Naidenko
Olga V
OV
Liu
Jin-huan
JH
Zhang
Rongguang
R
Joachimiak
Andrzej
A
Kronenberg
Mitchell
M
Cheroutre
Hilde
H
Reinherz
Ellis L
EL
Wang
Jia-huai
JH
D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*
D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; C028388:thymus-leukemia antigens