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- Title
Glycolipids with nonreducing end α-mannosyl residues that have the potential to activate invariant Vα19 NKT cells.
- Authors
Shimamura, Michio; Yi-Ying Huang; Okamoto, Naoki; Watanabe, Yutaka; Murakami, Yoshiko; Kinoshita, Taroh; Hirabayashi, Yoshio; Murakata, Chikara; Ito, Yukishige; Ogawa, Tomoya
- Abstract
We have previously demonstrated that α-mannosyl ceramide and its derivatives promote immune responses of NK1.1+ invariant Vα19-Jα33 T cell receptor (TCR) α+ T cells (Vα19 NKT cells). In this study, attempts were made to determine the structural requirements for natural ligands for Vα19 NKT cells. Naturally occurring and synthetic glycolipids were analyzed for their ability to stimulate the cells prepared from invariant Vα19-Jα33 TCR transgenic mice, in which development of Vα19 NKT cells is facilitated. As a result, α-mannosyl phosphatidylinositols such as 2,6-di-α-mannosyl phosphatidylinositol and α-mannosyl-4α-glucosaminyl-6-phosphatidylinositol (α-Man-GlcNH2-PtdIns) as well as α-mannosyl ceramide derivatives were found to activate the cells from the transgenic mouse liver, gut lamina propria and spleen in vivo and in vitro. Thus, glycolipids with nonreducing end α-mannosyl residues are suggested to be potent antigens for Vα19 NKT cells. Next, a series of invariant Vα19-Jα33 TCR+ hybridomas, each with variations in the sequence of the Vα-Jα junction and the TCR β chain, were tested for responsiveness toward the α-mannosyl glycolipids. A loose correlation between the primary structure of the TCR and the reactive glycolipids was observed. For instance, hybridomas expressing TCRs consisting of an α chain with a variation in the Vα19-Jα33 junction and a Vβ6+β chain showed affinity towards α-mannosyl ceramide and α-Man-GlcNH2-PtdIns, whereas those expressing TCRs with an invariant Vα19-Jα33 α chain and a Vβ8+β chain responded to 2,6-di-α-mannosyl phosphatidylinositol. Thus, it is suggested that Vα19 NKT cells with microheterogeneity in the TCR structure have been generated for defense against various antigens expressing α-mannosyl glycolipids.
- Subjects
GLYCOLIPIDS; GLYCOCONJUGATES; IMMUNE response; KILLER cells; T cell receptors; TRANSGENIC mice
- Publication
FEBS Journal, 2007, Vol 274, Issue 11, p2921
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2007.05826.x