Structural basis of mycobacterium tuberculosis lipid antigen-CD1b complex recognition by T cell receptor — ASN Events
  1. Schedule
  2. Session 5 - Antigen Recognition
  3. Structural basis of mycobacterium tuberculosis lipid antigen-CD1b complex recognition by T cell receptor

Structural basis of mycobacterium tuberculosis lipid antigen-CD1b complex recognition by T cell receptor (#38)

Stephanie Gras 1 2 , Adam Shahine 1 , Lynn L Tan , Ildiko Van Rhijn 3 4 , Dale Godfrey 5 6 , Branch Moody 3 , Jamie Rossjohn 1 2 7
  1. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Victoria, Australia
  2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia
  3. Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  4. Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
  5. Microbiology abd Immunology, UNiversity of Melbourne, Parkville, Vic, Australia
  6. ARC Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Victoria, Australia
  7. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, United Kingdom

Recently, we have identified CD1b-reactive T cells recognising mycobacterium tuberculosis lipid antigen, namely glucose monomycolate (GMM) using tetramer staining (Van Rhijn et al., 2013, Nature Immunology). We have isolated two sub-families of CD1b-GMM reactive T cells, exhibiting either high or low affinity. Sequence analysis of those high and low affinity TCRs, revealed a skewed TCR repertoire with a TRAV1-2 bias usage characteristic of the high affinity TCRs while a TRAV17 bias usage characterised the low affinity TCRs (Van Rhijn et al., 2014, Journal of Immunology).

Surprisingly the TRAV1-2 high affinity TCRs have a nearly invariant CDR3α sequences composed mainly of germline residues, therefore we named those receptors germline-encoded mycolyl-reactive or GEM TCRs. We have shown that the GEM TCRs exhibit an unusually high affinity of ~1 μM for CD1b-GMM.

To further understand the molecular basis of CD1b-GMM recognition by TCRs, as well as to determine the role played by the different Vα chains (TRAV1-2 and TRAV17) in TCR affinity, we performed a structural investigation of the CD1b-GMM in complex with a GEM TCR. The GEM TCRs will provide insight into a simplified CD1b-specific T cell repertoire and a specific understanding of T cell immunity from tuberculosis patients.