Characterisation of CD1a-restricted T cells using CD1a-lipid tetramers — ASN Events
  1. Schedule
  2. Poster Session Three
  3. Characterisation of CD1a-restricted T cells using CD1a-lipid tetramers

Characterisation of CD1a-restricted T cells using CD1a-lipid tetramers (#340)

Catriona V Nguyen-Robertson 1 2 , Michael NT Souter 1 2 , Scott JJ Reddiex 1 2 , Janice MH Cheng 1 2 3 , Adam P Uldrich 1 2 , Jamie Rossjohn 4 5 , Ildiko Van Rhijn 6 , Spencer J Williams 3 , D Branch Moody 6 , Dale I Godfrey 1 2 , Daniel G Pellicci 1 2
  1. The Department of Microbiology and Immunology, The Doherty Institute, The University of Melbourne, Parkville, Victoria, Australia
  2. ARC Centre of Excellence in Advanced Molecular Imaging at The University of Melbourne, Parkville, Victoria, Australia
  3. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
  4. ARC Centre of Excellence in Advanced Molecular Imaging at Monash University, Clayton, Victoria, Australia
  5. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  6. Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy and Harvard Medical School, Boston, MA, USA

In contrast to conventional T cells that recognise peptide antigens presented by proteins encoded in the major histocompatibility complex (MHC), other T cells recognise lipid antigens presented by MHC-like CD1 family members, CD1a, CD1b, CD1c and CD1d. Recent studies have suggested that CD1a-restricted T cells comprise a unique T cell population in human blood and may also play a unique functional role in skin. Here, we have produced mammalian CD1a tetramers to investigate the phenotype and function of human CD1a-restricted T cells directly ex vivo. Interestingly, we have shown that CD1a-restricted T cells that recognise non-self lipid antigens can also be self-reactive. Additionally, we have defined the T cell receptor (TCR) usage of both self- and foreign-lipid-reactive CD1a-restricted T cells, demonstrating that while they exhibit a diverse TCR repertoire, there is some biased variable gene usage. Experiments with CD1a mutant cell lines revealed that different TCRs can bind across the entire binding cleft of CD1a, which is likely to increase the diversity of lipid antigens that can be recognised by CD1a-restricted T cells. Phenotypic analyses of these cells revealed that they are negative for IL-18R and CD161, markers typically used to define other unconventional, innate-like T cells, such as type I NKT cells and MAIT cells, thereby distinguishing CD1a-restricted T cells from other unconventional T cells. Collectively, these studies represent an important step forward in characterising CD1a-restricted T cells, and further understanding their role in human health and disease.

#ASI2017QLD