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Nature Immunology 9, 777–784 (1 July 2008) | doi:10.1038/ni.1620

An autonomous CDR3|[delta]| is sufficient for recognition of the nonclassical MHC class I molecules T10 and T22 by |[gamma]||[delta]| T cells

Erin J Adams , Pavel Strop , Sunny Shin , Yueh-Hsiu Chien & K Christopher Garcia

It remains unclear whether γ|[delta]| T cell antigen receptors (TCRs) detect antigens in a way similar to antibodies or αβ TCRs. Here we show that reactivity between the G8 and KN6 γ|[delta]| TCRs and the major histocompatibility complex class Ib molecule T22 could be recapitulated, with retention of wild-type ligand affinity, in an αβ TCR after grafting of a G8 or KN6 complementarity-determining region 3-|[delta]| (CDR3|[delta]|) loop in place of the CDR3α loop of an αβ TCR. We also found that a shared sequence motif in CDR3|[delta]| loops of all T22-reactive γ|[delta]| TCRs bound T22 in energetically distinct ways, and that T10d, which bound G8 with weak affinity, was converted into a high-affinity ligand by a single point mutation. Our results demonstrate unprecedented autonomy of a single CDR3 loop in antigen recognition.