Journal article

Lipidomic scanning of self-lipids identifies headless antigens for natural killer T cells

Tan-Yun Cheng, T Praveena, Srinath Govindarajan, Catarina F Almeida, Daniel G Pellicci, Wellington C Arkins, Ildiko Van Rhijn, Koen Venken, Dirk Elewaut, Dale I Godfrey, Jamie Rossjohn, D Branch Moody

Proceedings of the National Academy of Sciences of the United States of America | National Academy of Sciences | Published : 2024

Abstract

To broadly measure the spectrum of cellular self-antigens for natural killer T cells (NKT), we developed a sensitive lipidomics system to analyze lipids trapped between CD1d and NKT T cell receptors (TCRs). We captured diverse antigen complexes formed in cells from natural endogenous lipids, with or without inducing endoplasmic reticulum (ER) stress. After separating protein complexes with no, low, or high CD1d-TCR interaction, we eluted lipids to establish the spectrum of self-lipids that facilitate this interaction. Although this unbiased approach identified fifteen molecules, they clustered into only two related groups: previously known phospholipid antigens and unexpected neutral lipid a..

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