3MBE

TCR 21.30 in complex with MHC class II I-Ag7HEL(11-27)

Summary for 3MBE

• Entry DOI: 10.2210/pdb3mbe/pdb
• Descriptor: MHC CLASS II H2-IAg7 ALPHA CHAIN, MHC CLASS II H2-IAg7 BETA CHAIN, PEPTIDE HEL 11-27, ... (7 entities in total)
• Functional Keywords: t cell receptor, histocompatability antigen, mhc class ii, i-ag7, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 10
• Total formula weight: 203930.53

Authors

Corper, A.L.,Yoshida, K.,Teyton, L.,Wilson, I.A. (deposition date: 2010-03-25, release date: 2010-05-12, Last modification date: 2024-11-20)

Primary citation

Yoshida, K.,Corper, A.L.,Herro, R.,Jabri, B.,Wilson, I.A.,Teyton, L.
The diabetogenic mouse MHC class II molecule I-Ag7 is endowed with a switch that modulates TCR affinity.
J.Clin.Invest., 120:1578-1590, 2010

PubMed Abstract: Genetic susceptibility to autoimmunity is frequently associated with specific MHC alleles. Diabetogenic MHC class II molecules, such as human HLA-DQ8 and mouse I-Ag7, typically have a small, uncharged amino acid residue at position 57 of their beta chain (beta57); this results in the absence of a salt bridge between beta57 and Argalpha76, which is adjacent to the P9 pocket of the peptide-binding groove. However, the influence of Argalpha76 on the selection of the TCR repertoire remains unknown, particularly when the MHC molecule binds a peptide with a neutral amino acid residue at position P9. Here, we have shown that diabetogenic MHC class II molecules bound to a peptide with a neutral P9 residue primarily selected and expanded cells expressing TCRs bearing a negatively charged residue in the first segment of their complementarity determining region 3beta. The crystal structure of one such TCR in complex with I-Ag7 bound to a peptide containing a neutral P9 residue revealed that a network of favorable long-range (greater than 4 A) electrostatic interactions existed among Argalpha76, the neutral P9 residue, and TCR, which supported the substantially increased TCR/peptide-MHC affinity. This network could be modulated or switched to a lower affinity interaction by the introduction of a negative charge at position P9 of the peptide. Our results support the existence of a switch at residue beta57 of the I-Ag7 and HLA-DQ8 class II molecules and potentially link normal thymic TCR selection with abnormal peripheral behavior.

PubMed: 20407212
DOI: 10.1172/JCI41502

Experimental method

X-RAY DIFFRACTION (2.886 Å)