|3t0e, resolution 4.00Å ()|
|Gene:||HLA-DRA, HLA-DRA1 (Homo sapiens), HLA-DRB1 (Homo sapiens), CD4 (Homo sapiens)|
Crystal structure of a complete ternary complex of T cell receptor, peptide-MHC and CD4
Adaptive immunity depends on specific recognition by a T-cell receptor (TCR) of an antigenic peptide bound to a major histocompatibility complex (pMHC) molecule on an antigen-presenting cell (APC). In addition, T-cell activation generally requires binding of this same pMHC to a CD4 or CD8 coreceptor. Here, we report the structure of a complete TCR-pMHC-CD4 ternary complex involving a human autoimmune TCR, a myelin-derived self-peptide bound to HLA-DR4, and CD4. The complex resembles a pointed arch in which TCR and CD4 are each tilted approximately 65 degrees relative to the T-cell membrane. By precluding direct contacts between TCR and CD4, the structure explains how TCR and CD4 on the T cell can simultaneously, yet independently, engage the same pMHC on the APC. The structure, in conjunction with previous mutagenesis data, places TCR-associated CD3epsilongamma and CD3epsilondelta subunits, which transmit activation signals to the T cell, inside the TCR-pMHC-CD4 arch, facing CD4. By establishing anchor points for TCR and CD4 on the T-cell membrane, the complex provides a basis for understanding how the CD4 coreceptor focuses TCR on MHC to guide TCR docking on pMHC during thymic T-cell selection.
Crystal structure of a complete ternary complex of T-cell receptor, peptide-MHC, and CD4., Yin Y, Wang XX, Mariuzza RA, Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5405-10. Epub 2012 Mar 19. PMID:22431638
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.