Structure of a γδ T Cell Receptor in Complex with the Nonclassical MHC T22

γδ T cell receptors (TCRs), αβ TCRs, and antibodies are the three lineages of somatically recombined antigen receptors. The structural basis for ligand recognition is well defined for αβ TCR and antibodies but is lacking for γδ TCRs. We present the 3.4 Å structure of the murine γδ TCR G8 bound to its major histocompatibility complex (MHC) class Ib ligand, T22. G8 predominantly uses germline-encoded residues of its δ chain complementarity-determining region 3 (CDR3) loop to bind T22 in an orientation substantially different from that seen in αβ TCR/peptide-MHC. That junctionally encoded G8 residues play an ancillary role in binding suggests a fusion of innate and adaptive recognition strategies.

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