| Affiliations | Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Parkville, Victoria 3010, Australia; Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia; Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, Netherlands; School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, England, UK; Department of Chemistry, University of Connecticut, Storrs, CT 06269; Istituto Giannina Gaslini, 161... | |
| Abstract | and T cells are disparate T cell lineages that can respond to distinct antigens (Ags) via the use of the and T cell Ag receptors (TCRs), respectively. Here we characterize a population of human T cells, which we term / T cells, expressing TCRs comprised of a TCR- variable gene (V1) fused to joining and constant domains, paired with an array of TCR- chains. We demonstrate that these cells, which represent ∼50% of all V1(+) human T cells, can recognize peptide- and lipid-based Ags presented by human leukocyte antigen (HLA) and CD1d, respectively. Similar to type I natural killer T (NKT) cells, CD1d-lipid Ag-reactive / T cells recognized -galactosylceramide (-GalCer); however, their fine specificity for other lipid Ags presented by CD1d, such as -glucosylceramide, was distinct from type I NKT cells. Thus, /TCRs contribute new patterns of Ag specificity to the human immune system. Furthermore, we provide the molecular bases of how /TCRs bind to their targets, with the V1-encoded region providing a major contribution to /TCR binding. Our findings highlight how components from and TCR gene loci can recombine to confer Ag specificity, thus expanding our understanding of T cell biology and TCR diversity. | |