An Autonomous CDR3δ is Sufficient for γδ T Cell Recognition of the Nonclassical MHC-I T10/T22

It remains unclear whether γδ T cell receptors (TCRs) detect antigens in a manner similar to antibodies or αβ TCRs. Here we show that reactivity between G8 and KN6 γδ TCRs and the MHC class Ib molecule T22 can be transplanted, with retention of wild-type ligand affinity, after en bloc grafting of G8 and KN6 CDR3δ loops in place onto the CDR3α loop of an αβ TCR. We also find that a shared sequence motif within CDR3δ loops of all T22-reactive γδ TCRs binds T22 in energetically distinct fashions, and that T10d, which binds G8 with weak affinity, is converted into a high-affinity ligand by a single point mutation. These results demonstrate an unprecedented autonomy of a single CDR3 loop in antigen recognition. Disciplines Cell Biology | Microbiology | Pathogenic Microbiology | Virology Comments At the time of publication, author Sunny Shin was affiliated with Stanford University School of Medicine. Currently, she is a faculty member at the Department of Microbiology at the University of Pennsylvania. This journal article is available at ScholarlyCommons: http://repository.upenn.edu/microbiology/7 An autonomous CDR3δ is sufficient for γδ T cell recognition of the nonclassical MHC-I T10/T22 Erin J Adams1,*, Pavel Strop2, Sunny Shin3, Yueh-Hsiu Chien3, and K Christopher Garcia2,4,* 1Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA 2Departments of Molecular & Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA 3Department of Microbiology & Immunology and Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA 4Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA