A structural investigation into CD1b-autoreactive αβ T-cell receptors — ASN Events
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A structural investigation into CD1b-autoreactive αβ T-cell receptors (#144)

Adam Shahine 1 2 , Ildiko V Rhijn 3 , Lynn Tan 1 , Dale Godfrey 2 4 , Branch Moody 5 , Stephanie Gras 1 2 , Jamie Rossjohn 1 2 6
  1. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  2. Australian Research Council Center of Excellence in Advanced Molecular Imaging, Melbourne
  3. Department of Infectious Diseases and Immunology, University Utrecht, Utrecht, Netherlands
  4. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia
  5. Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  6. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, Wales, UK

Central to both systems of innate and adaptive immunity is the T-cell recognition of antigen-presenting molecules presenting antigens (Ag) by T-cell receptors (TCR). The CD1 molecules are Major Histocompatibility Complex (MHC) class 1 like molecules involved in the presentation of foreign and self-lipid antigens. CD1b is a member of group 1 CD1 molecules, and exhibits the largest hydrophobic binding pocket of the CD1 molecules, allowing it the capabilities of presenting a broad repertoire of self and mycobacterial lipids of varying tail lengths.

Using tetramers of CD1b presenting phospholipids, two αβ TCRs have recently been identified (van Rhijn et al., unpublished), termed PG90 and PG10. They were found to be reactive to CD1b presenting a number of endogenous phospholipids with varying affinities, including a number of non-binding phospholipids. Despite both recognizing phospholipids, the PG90 and PG10 TCRs are different in sequence (TRAV6-1/TRBV7-8 and TRAV13-1/TRBV4-1 respectively), which might ultimately contribute to differing fine specificities for an array of phospholipids.

Here we have expressed and refolded the PG90 and PG10 TCRs and characterized the affinities of the TCRs for a range of phospholipids presented by CD1b via surface plasmon resonance (SPR). We have determined the structures of the TCRs alone and the CE1b presenting a range of phospholipids to understand TCR recognition and fine specificities of these 2 TCRs.