[HTML][HTML] How a single T cell receptor recognizes both self and foreign MHC

LA Colf, AJ Bankovich, NA Hanick, NA Bowerman… - Cell, 2007 - cell.com
LA Colf, AJ Bankovich, NA Hanick, NA Bowerman, LL Jones, DM Kranz, KC Garcia
Cell, 2007cell.com
Summary αβ 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 Å 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 …
Summary
αβ 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 Å structure of the 2C TCR complexed with its foreign ligand H-2Ld-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-2Kb-dEV8. 2C engages both shared and polymorphic residues on Ld and Kb, as well as the unrelated QL9 and dEV8 peptide antigens, in unique pair-wise contacts, resulting in greater structural complementarity with the Ld-QL9 complex. In the structure of an engineered, high-affinity 2C TCR variant bound to H-2Ld-QL9, the "wild-type" TCR-MHC binding orientation persists despite modified TCR-CDR3α 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.
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