Enhanced CD1d phosphatidylserine presentation using a single-domain antibody promotes immunomodulatory CD1d-TIM-3 interactions.

"the crystal structure has been deposited in the protein data bank vhh1d17-hcd1d(sphingomyelin) (pdb accession code: 8sos;doi: https://doi org/10 2210/pdb8sos/pdb )."

"Competing interests: DLH, PB and HJvdV are employees of LAVA Therapeutics, a company that develops bispecific gamma-delta T-cell engagers, and own LAVA Therapeutics shares and/or stock options. RL, TDdG and HJvdV are named inventors on international patent application WO 2016/122320 Al (‘Single domain antibodies targeting CD1d’) which partially relates to the work described in this paper. TDdG is a consultant for and a shareholder of LAVA Therapeutics. RL and MV were funded by a LAVA Therapeutics grant to Amsterdam UMC. JR has received funding from LAVA Therapeutics. DIG is a member of the scientific advisory board and a shareholder of Avalia Immunotherapies, a company working on NKT cell-based vaccines and is an inventor on patent applications WO 2021/127745 and WO 2021/127744 that describe effects of cross-linking CD1 molecules and WO2020/231274 that describes CD1d-dependent glycopeptide vaccines."

"Funding: This work was supported by CCA-VICI grant no. 2000483 from the VU University Medical Center, grant no. 140343 from Worldwide Cancer Research, funding from LAVA Therapeutics (RL, MV, DLH, PB and HJvdV), the National Health and Medical Research Council of Australia (NHMRC; grant nos. 1113293 and 1140126), and the Cancer Council of Victoria (JR and DIG). DIG was supported by an NHMRC Senior Principal Research Fellowship (no. 1117766) and subsequently by an NHMRC Investigator Award (2008913). JR is supported by an NHMRC Investigator award. AS is supported by an ARC DECRA Fellowship (DE210101031). We thank the Monash Macromolecular Crystallization Facility staff for assistance with crystallization, the Australian Synchrotron for assistance with data collection, the University of Melbourne, Department of Microbiology and Immunology Flow Cytometry facility for flow cytometry support, and Dr Adam P Uldrich for providing the SKW-3.NKT12 and SKW-3.NKT15 cells and the C1R.GFP cells expressing WT CD1d or mutant CD1d."