2E7L

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

Summary for 2E7L

• Entry DOI: 10.2210/pdb2e7l/pdb
• Related: 2OI9
• Descriptor: Cytotoxic Tcell receptor, Beta-chain, H-2 class I histocompatibility antigen, L-D alpha chain, ... (5 entities in total)
• Functional Keywords: tcr, mhc, immune system
• Biological source: Mus musculus (house mouse); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01897
• Total number of polymer chains: 8
• Total formula weight: 96470.72

Authors

Garcia, K.C.,Colf, L.A. (deposition date: 2007-01-11, release date: 2007-04-24, Last modification date: 2024-10-16)

Primary citation

Colf, L.A.,Bankovich, A.J.,Hanick, N.A.,Bowerman, N.A.,Jones, L.L.,Kranz, D.M.,Garcia, K.C.
How a single T cell receptor recognizes both self and foreign MHC.
Cell(Cambridge,Mass.), 129:135-146, 2007

PubMed Abstract: alphabeta T cell receptors (TCRs) can crossreact with both self- and foreign- major histocompatibility complex (MHC) proteins in an enigmatic phenomenon termed alloreactivity. Here we present the 2.35 A structure of the 2C TCR complexed with its foreign ligand H-2L(d)-QL9. Surprisingly, we find that this TCR utilizes a different strategy to engage the foreign pMHC in comparison to the manner in which it recognizes a self ligand H-2K(b)-dEV8. 2C engages both shared and polymorphic residues on L(d) and K(b), as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the L(d)-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2L(d)-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3alpha interactions with peptide. Thus, a single TCR recognizes two globally similar, but distinct ligands by divergent mechanisms, indicating that receptor-ligand crossreactivity can occur in the absence of molecular mimicry.

PubMed: 17418792
DOI: 10.1016/j.cell.2007.01.048

Experimental method

X-RAY DIFFRACTION (2.5 Å)