Characterisation and Development of unconventional T cells — ASN Events
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  2. Symposium III: Mucosal Immunology
  3. Characterisation and Development of unconventional T cells

Characterisation and Development of unconventional T cells (#51)

Hui-Fern Koay 1 , Catriona V Nguyen-Robertson 1 2 , Michael NT Souter 1 2 , Scott JJ Reddiex 1 2 , Shian Su 3 , Daniela Zalcenstein 3 , Cyril Seillet 3 , Catarina F Almeida 1 , Chris Harpur 1 , Anselm Enders 4 , Auda A Eltahla 5 , Fabio Luciani 5 , Janice MH Cheng 1 2 6 , Oanh Nguyen 1 , Katherine Kedzierska 1 , Jamie Rossjohn 7 8 9 , Yves d’Udekem 10 , Igor E Konstantinov 10 , Tan-Yun Cheng 11 , Ildiko van Rhijn 11 , James McCluskey 1 , Adam P Uldrich 1 2 , Gabrielle T Belz 3 , Spencer J Williams 6 , Stuart P Berzins 12 13 , Branch D Moody 11 , Dale I Godfrey 1 2 , Daniel Pellicci 1
  1. Microbiology and Immunology, University of Melbourne, Parkville, VIC, Australia
  2. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, University of Melbourne, Parkville, VIC, Australia
  3. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
  4. The John Curtin School of Medical Research, Department of Immunology, Canberra, Australia
  5. School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
  6. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia
  7. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  8. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK
  9. Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia
  10. Royal Children’s Hospital, Flemington Road, Parkville, Australia
  11. Brigham and Women's Hospital Division of Rheumatology, Immunology and Allergy, Harvard Medical School, Boston, Massachusetts, USA
  12. Collaborative Research Network, Federation University, Ballarat, Australia
  13. Fiona Elsey Cancer Research Institute, Ballarat, Australia

Most studies on T cells have focused on conventional T cells that respond to peptides from viruses, bacteria and other pathogens. However, the human immune system contains large populations of unconventional T cells that recognise lipid antigens or Vitamin B derivatives presented by CD1 and MR1 molecules, respectively. Surprisingly, little is known about the role of these T cells in human immunity, largely owing to a lack of specific reagents to identify these cells. We have produced CD1 tetramers that contain endogenous mammalian lipid antigens or antigen-specific CD1 tetramers that contain lipid antigens derived from Mycobacterium tuberculosis (Mtb). We show that we can clearly identify both endogenous and Mtb reactive CD1 tetramer positive cells from healthy human blood. Moreover, using MR1 tetramers, we identify previously undescribed populations of Mucosal-Associated Invariant T (MAIT) cells within mouse and human thymus. We use a combination of multicolour flow cytometry, RNA-seq and gene deficient mice to characterise these poorly understood unconventional T cell populations and provide novel insight into the molecular mechanisms that underpin their development and function.

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