Poster Presentation Lorne Infection and Immunity 2023

Characterisation of CD1c-restricted T cells recognising mycobacterial lipids (#197)

Caroline Soliman 1 , Katrina J Smith 1 , Samuel J Redmond 1 , D Branch Moody 2 , Dale I Godfrey 1 , Nicholas A Gherardin 1
  1. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Parkville, Victoria, Australia
  2. Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

The CD1 family are MHC I-like molecules that present self and foreign lipid antigens to T cells. CD1a, CD1b and CD1c are known for their presentation of lipids derived from the Mycobacterium tuberculosis (Mtb) cell wall, and CD1-restricted T cells are thought to play an important role in the immune response toward Mtb as well as the Bacillus Calmette–Guérin (BCG) vaccine. CD1c in particular has been shown to present mycoketide lipids including phosphomycoketide (PM) and mannosyl phosphomycoketide (MPM). However, little is known about the T cells that respond to these lipids. This is partly due to the fact that CD1c-restricted T cells are not present in mice, making them harder to study. In addition, until recently, the use of CD1c-lipid tetramers has been obfuscated by their reactivity toward receptors from the broadly expressed CD36 family, limiting their use for detecting T cell receptor (TCR)-specific staining in blood samples. Here, through the use of CD1c tetramers in conjunction with CD36 blocking antibodies, we isolate CD1c-restricted T cells ex vivo from human blood, and characterise them in the context of their lipid reactivity profile. Intriguingly, CD1c-PM restricted T cells are particularly abundant relative to CD1c-MPM and CD1c-autoreactive cells. These cells display a fine-specificity for PM, with minimal cross-reactivity to other lipids. The surface phenotype of these cells is generally diverse with CD1c-reactivity extending to both αβ and γδ T cells, and spread across CD4, CD8 and double negative αβ T cell populations. Their TCR repertoire is also diverse, with a TRBV gene bias. Furthermore, analysis of memory subsets suggests these cells may follow adaptive-like dynamics. By understanding the specificity and functionality of these cells, we aim to explore the unique role that CD1c-restricted T cells play in the immune system, and begin elucidating their uses as potential immunotherapeutic agents against foreign targets.