A T cell receptor CDR3beta loop undergoes conformational changes of unprecedented magnitude upon binding to a peptide/MHC class I complex.

The elongated complementary-determining region (CDR) 3beta found in the unliganded KB5-C20 TCR protrudes from the antigen binding site and prevents its docking onto the peptide/MHC (pMHC) surface according to a canonical diagonal orientation. We now present the crystal structure of a complex involving the KB5-C20 TCR and an octapeptide bound to the allogeneic H-2K(b) MHC class I molecule. This structure reveals how a tremendously large CDR3beta conformational change allows the KB5-C20 TCR to adapt to the rather constrained pMHC surface and achieve a diagonal docking mode. This extreme case of induced fit also shows that TCR plasticity is primarily restricted to CDR3 loops and does not propagate away from the antigen binding site.