Benzofuran sulfonates and small self-lipid antigens activate type II NKT cells via CD1d

Catarina F Almeida; Dylan GM Smith; Tan-Yun Cheng; Chris M Harpur; Elena Batleska; Catriona V. Nguyen-Robertson; Tram Nguyen; Tamara Thelemann; Scott JJ Reddiex; Shihan Li; Sidonia BG Eckle; Ildiko Van Rhijn; Jamie Rossjohn; Adam P Uldrich; D Branch Moody; Spencer J Williams; Daniel G Pellicci; Dale Godfrey

Journal article

Benzofuran sulfonates and small self-lipid antigens activate type II NKT cells via CD1d

Catarina F Almeida, Dylan GM Smith, Tan-Yun Cheng, Chris M Harpur, Elena Batleska, Catriona V. Nguyen-Robertson, Tram Nguyen, Tamara Thelemann, Scott JJ Reddiex, Shihan Li, Sidonia BG Eckle, Ildiko Van Rhijn, Jamie Rossjohn, Adam P Uldrich, D Branch Moody, Spencer J Williams, Daniel G Pellicci, Dale Godfrey

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2021

DOI: 10.1073/pnas.2104420118

Abstract

Natural killer T (NKT) cells detect lipids presented by CD1d. Most studies focus on type I NKT cells that express semi-invariant αβ T cell receptors (TCR) and recognize α-galactosylceramides. However, CD1d also presents structurally distinct lipids to NKT cells expressing diverse TCRs (type II NKT cells), but our knowledge of the antigens for type II NKT cells is limited. An early study identified a nonlipidic NKT cell agonist, phenyl pentamethyldihydrobenzofuransulfonate (PPBF), which is notable for its similarity to common sulfa drugs, but its mechanism of NKT cell activation remained unknown. Here, we demonstrate that a range of pentamethylbenzofuransulfonates (PBFs), including PPBF, acti..

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University of Melbourne Researchers

Dale Godfrey Author Microbiology and Immunology

Catarina Dos Santos Sa E Almeida Author Microbiology and Immunology

Adam Uldrich Author Microbiology and Immunology

Daniel Pellicci Author Microbiology and Immunology

Spencer Williams Author Chemistry

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Grants

Awarded by Australian Research Council (ARC)

Awarded by National Health and Medical Research Council of Australia (NHMRC)

Awarded by NIH

Awarded by ARC Discovery Early Career Research Award Fellowship

Awarded by Future Felloship

Awarded by NHMRC Senior Principal Research Fellowship

Funding Acknowledgements

We are grateful to Dr. Paul Savage (Brigham Young University, Provo, UT) for providing the alpha-GalCer analogue PBS44 used for production of CD1d-alpha-GalCer tetramers. We thank the staff from the flow cytometry facilities at the Department of Microbiology and Immunology at the Peter Doherty Institute and the Melbourne Brain Centre at the University of Melbourne. This work was supported by the Australian Research Council (ARC; DP170104386, DP210100235, and CE140100011) , the National Health and Medical Research Council of Australia (NHMRC; 1113293, 1083885, and 1145373) , the NIH (R01 AR048632 and AI049313) , the Allergy and Immunology Foundation of Australia (C.F.A., 2021) , and the University of Melbourne (Early Career Researcher Grant; C.F.A., 2021) . S.B.G.E. is supported by ARC Discovery Early Career Research Award Fellowship DE170100407. J.R. is supported by an ARC Australian Laureate Fellowship. A.P.U. was supported by a Future Fellow-ship (FT140100278) . D.G.P. is supported by a CSL Centenary Fellowship. D.I.G. is supported by an NHMRC Senior Principal Research Fellowship (1117766) .