3T0E

Crystal structure of a complete ternary complex of T cell receptor, peptide-MHC and CD4

Summary for 3T0E

• Entry DOI: 10.2210/pdb3t0e/pdb
• Related: 3O6F
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, HLA class II histocompatibility antigen, DRB1-4 beta chain, T-cell receptor alpha chain, ... (5 entities in total)
• Functional Keywords: cd4, t cell receptor, tcr, hla class ii, mhc, autoimmunity, t cell activation, immunoglobulin fold, immune system, membrane
• Biological source: Homo sapiens (human); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P01903 P13760 P01730
• Total number of polymer chains: 5
• Total formula weight: 138315.22

Authors

Yin, Y.,Mariuzza, R.A. (deposition date: 2011-07-20, release date: 2012-03-07, Last modification date: 2024-10-30)

Primary citation

Yin, Y.,Wang, X.X.,Mariuzza, R.A.
Crystal structure of a complete ternary complex of T-cell receptor, peptide-MHC, and CD4.
Proc.Natl.Acad.Sci.USA, 109:5405-5410, 2012

PubMed Abstract: 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 ∼65° 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 CD3εγ and CD3εδ 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.

PubMed: 22431638
DOI: 10.1073/pnas.1118801109

Experimental method

X-RAY DIFFRACTION (4 Å)