2OI9

Structure of the 2C/Ld/QL9 allogeneic complex

Summary for 2OI9

• Entry DOI: 10.2210/pdb2oi9/pdb
• Related: 2E7L
• Descriptor: Major Histocompatibility Complex protein, T cell receptor alpha chain, T cell receptor beta 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: 4
• Total formula weight: 47760.69

Authors

Garcia, K.C.,Colf, L.A. (deposition date: 2007-01-10, release date: 2007-04-24, Last modification date: 2024-10-30)

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 (2.35 Å)