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Unconventional lipid-antigen recognition by group 1 CD1 restricted T cells
TItle: Unconventional lipid-antigen recognition by group 1 CD1 restricted T cells
Brief description: Beyond peptides, lipid antigens are presented to T cells by the CD1 family of antigen-presenting molecules, providing a parallel system of immune surveillance that has been less explored than peptide-MHC recognition. While CD1d-restricted natural killer T (NKT) cells and their T cell receptor (TCR) recognition mechanisms are well characterised, far less is known about how the group 1 CD1 molecules (CD1a, CD1b, and CD1c) present lipids and engage diverse TCR repertoires, leaving lipid-reactive immunity incompletely understood. Early models of lipid antigen presentation assumed close analogy to peptide-MHC recognition, with antigens displayed in an upright, end-to-end orientation for TCR engagement. However, structural studies demonstrate that group 1 CD1 molecules use broader and more flexible antigen display strategies to accommodate a wide range of self- and foreign- lipid antigens. Notably, we identified a non-canonical CD1c mechanism in which bulky lipid antigens are displayed in a sideways orientation, challenging long-standing assumptions about antigen presentation and immune surveillance. Using X-ray crystallography, structural computation, and more recently cryo- electron microscopy, we have defined multiple modes of TCR engagement across CD1a, CD1b, and CD1c, including lipid co-recognition and lipid-independent docking, and uncovered public and gene-biased TCR docking mechanisms. Together, these findings revise classical models of lipid antigen presentation and raise fundamental questions about how distinct display modes shape T cell specificity and function in immunity.
Short bio: Dr Adam Shahine is a mid-career researcher and currently an NHMRC Emerging Leadership Fellow within the Department of Biochemistry and Molecular Biology at the Monash Biomedicine Discovery Institute (BDI), Melbourne, Australia. He obtained his PhD in Biochemistry in 2016 and has since undergone postdoctoral training both in Monash (Aus) and Cardiff University (UK). In 2023, he was appointed as a BDI group leader, where his group focuses on the molecular characterisation of lipid antigen presentation and processing by group 1 CD1 molecules to T cells. His research predominantly focuses on establishing the molecular determinants of lipid antigen presentation by each CD1 member, the models of unconventional lipid mediated T cell receptor recognition, and in the context of disease, the role of lipid presentation in M. tuberculosis infection and immune dysregulation in autoimmunity.
Date:
2 February 2026, 13:00
Venue:
This webinar is online, registration is required
Speaker:
Dr Adam Shahine (University of Monash)
Organising department:
MRC Weatherall Institute of Molecular Medicine
Organiser contact email address:
hashem.koohy@rdm.ox.ac.uk
Part of:
Unravelling T Cell Recognition: Insights from immunology and AI
Booking required?:
Required
Booking url:
https://bit.ly/49ETs2Q
Booking email:
hashem.koohy@rdm.ox.ac.uk
Cost:
0
Audience:
Public
Editor:
Hashem Koohy
