The molecular bases of ?/?? T cell-mediated antigen recognition.

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 (V?1) fused to joining ? and constant ? domains, paired with an array of TCR-? chains. We demonstrate that these cells, which represent ?50% of all V?1(+) 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 V?1-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.

SUBMITTER: Pellicci DG 

PROVIDER: S-EPMC4267242 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature