3E2H

Structure of the m67 high-affinity mutant of the 2C TCR in complex with Ld/QL9

Summary for 3E2H

• Entry DOI: 10.2210/pdb3e2h/pdb
• Related: 3E3Q
• Descriptor: H-2 class I histocompatibility antigen, L-D alpha chain, QL9 PEPTIDE, T-cell receptor alpha chain V region PHDS58, ... (4 entities in total)
• Functional Keywords: tcr, mhc, cross-reactivity, high affinity, glycoprotein, immune response, membrane, mhc i, phosphoprotein, transmembrane, immunoglobulin domain, receptor, immune system
• Biological source: Mus musculus (mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01897
• Total number of polymer chains: 4
• Total formula weight: 45726.60

Authors

Colf, L.A.,Garcia, K.C. (deposition date: 2008-08-05, release date: 2008-11-04, Last modification date: 2024-10-16)

Primary citation

Jones, L.L.,Colf, L.A.,Stone, J.D.,Garcia, K.C.,Kranz, D.M.
Distinct CDR3 Conformations in TCRs Determine the Level of Cross-Reactivity for Diverse Antigens, but Not the Docking Orientation
J.Immunol., 181:6255-6264, 2008

PubMed Abstract: T cells are known to cross-react with diverse peptide MHC Ags through their alphabeta TCR. To explore the basis of such cross-reactivity, we examined the 2C TCR that recognizes two structurally distinct ligands, SIY-K(b) and alloantigen QL9-L(d). In this study we characterized the cross-reactivity of several high-affinity 2C TCR variants that contained mutations only in the CDR3alpha loop. Two of the TCR lost their ability to cross-react with the reciprocal ligand (SIY-K(b)), whereas another TCR (m67) maintained reactivity with both ligands. Crystal structures of four of the TCRs in complex with QL9-L(d) showed that CDR1, CDR2, and CDR3beta conformations and docking orientations were remarkably similar. Although the CDR3alpha loop of TCR m67 conferred a 2000-fold higher affinity for SIY-K(b), the TCR maintained the same docking angle on QL9-L(d) as the 2C TCR. Thus, CDR3alpha dictated the affinity and level of cross-reactivity, yet it did so without affecting the conserved docking orientation.

PubMed: 18941216

Experimental method

X-RAY DIFFRACTION (3.8 Å)