Antigen recognition by γδ T cells
Dept. of Biochemistry and Molecular Biology
Biography:Dr. Adams completed her PhD at the University of California, Berkeley where she studied the molecular evolution of MHC molecules. She then pursued post-doctoral training at Stanford University in structural and molecular immunology. At the end of 2005, she started her own laboratory at the University of Chicago in the Biochemistry and Molecular Biology department, where she was recently promoted to full professor. Dr. Adams has authored over 70 publications in high-ranking journals, is on the editorial board of Immunogenetics.
Abstract:γδ T cells represent a significant proportion of T cells in humans yet the signals to which they respond have remained, for the most part, uncharacterized. Our laboratory is interested in identifying these signals and how they regulate γδ T cell activity in the tissues in which these cells reside. The majority of human γδ T cells express a T cell receptor (TCR) using a Vδ1, Vδ2 or Vδ3 domain. We have been examining the antigen-recognition capabilities of Vδ1 and Vδ2 (specifically Vγ9Vδ2 T cells) expressing T cells; these two major T cell subsets differ extensively in how they are regulated by antigenic signals. Our work and that of others has demonstrated an association between members of the CD1 family of lipid-presenting molecules and human Vδ1 TCR expressing γδ T cells, the major intestine-resident γδ population. We have predominantly focused on Vδ1 recognition of CD1d presenting the self-lipid sulfatide and have shown the biochemical and structural basis for this recognition and have further evidence that this is an important ligand for Vδ1 immune surveillance in the gut. Vγ9Vδ2 T cells, in contrast, predominate in human blood and are activated by target cells exposed to pyrophosphate containing small molecules called phosphoantigens. We have shown the critical role for the butyrophilin protein, BTN3A1, in this recognition process, demonstrating that phosphoantigens interact directly with BTN3A1’s intracellular B30.2 domain. How this translates into engagement of the Vγ9Vδ2 TCR is still unclear. Together, we provide functional, biochemical and structural insight into modulation of human γδ T cell activity by MHC-like and non-MHC molecules, demonstrating the diverse ways in which γδ T cells survey their environment for infection or dysregulation.
Time: Jun.16th.2015, 16:00
Venue: New Biology Building, Room 143
