ePoster Presentation 49th Annual Scientific Meeting of the Australian and New Zealand Society for Immunology 2021

CD1a-restricted T cells: a subset of “unconventional” T cells like no other (#169)

Catriona V Nguyen-Robertson 1 2 , Scott JJ Reddiex 3 , Willem Van Der Byl 4 , Michael NT Souter 1 2 , Janice MH Cheng 2 5 , Adam P Uldrich 1 2 , Jamie Rossjohn 6 7 , Ildiko Van Rhijn 8 , Spencer J Williams 2 5 , D Branch Moody 8 , Fabio Luciani 4 , Dale I Godfrey 1 2 , Daniel G Pellicci 3
  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. Murdoch Children's Research Institute, Parkville, Victoria, Australia
  4. Kirby Institute, University of New South Wales, Kensington, New South Wales, Australia
  5. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia
  6. ARC Centre of Excellence in Advanced Molecular Imaging at Monash University, Clayton, Victoria, Australia
  7. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia
  8. 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 MHC, a subset of “unconventional” T cells recognise lipid antigens presented by MHC-like CD1 family members: CD1a, CD1b, CD1c and CD1d. CD1a-restricted T cells is one such group that comprise a significant proportion of the peripheral T cell pool yet, compared to CD1d-restricted, natural killer T (NKT cells), relatively little is known about their role in the immune system.

We produced CD1a tetramers to investigate the phenotype and function of human CD1a-restricted T cells directly ex vivo. We isolated CD1a-restricted T cells that recognise non-self-lipid antigens, particularly dideoxymycobactin (DDM), a lipid from Mycobacterium tuberculosis. DDM is a potent activator of these T cells, suggestive of a role for these cells in mycobacterial immunity. We also isolated CD1a-restricted T cells that recognise to lipids from common dermatological products, suggestive of a possible contribution to skin allergy, as well as those that recognise self-lipid antigens.

Additionally, we 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 usage of variable genes. Experiments with CD1a mutant cell lines revealed that TCRs incorporating different variable genes have different binding patterns across the CD1a binding cleft, which likely increases the diversity of antigens that can be recognised by CD1a-restricted T cells.

Phenotypic analyses and RNA-sequencing of CD1a-restricted T cells revealed that they are distinct from CD1b- and CD1d-restricted T cells, distinguishing them as a unique population of unconventional T cells. They did not express innate-like markers such as CD161, IL-18R, and PLZF, but instead exhibited similar profiles to conventional CD4+ T cells. Collectively, these studies represent an important step forward in characterising CD1a-restricted T cells and further understanding their role in health and disease.