Poster Presentation CD1-MR1 2024

Characterisation of CD1c-restricted T cells in humans (#112)

Caroline Soliman 1 , Katrina J Smith 1 , Samuel J Redmond 1 , Zheng Ruan 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. CD1-restricted T cells are thought to play an important role in the immune response toward Mycobacterium tuberculosis (Mtb) and the Bacillus Calmette–Guérin (BCG) vaccine. CD1c in particular has been shown to present mycoketide lipids including phosphomycoketide (PM) and mannosyl phosphomycoketide (MPM), although little is known about the T cells that respond to them. CD1c-restricted T cells have been harder to study, partly because they are not present in mice. 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 blockade, we isolate these 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 αβT cell populations. Their TCR repertoire is also diverse, with a TRBV gene bias, as well as TRGV and TRDV gene bias’. Furthermore, CD1c-PM and CD1c-MPM restricted TCRs show varying degrees of lipid reactivity in in vitro cultures. 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.