tailieunhanh - Báo cáo khoa học: Glycolipids with nonreducing end a-mannosyl residues that have the potential to activate invariant Va19 NKT cells

We have previously demonstrated thata-mannosyl ceramide and its deriva-tives promote immune responses of + invariant Va19-Ja33 T cell receptor (TCR) a + T cells (Va19 NKT cells). In this study, attempts were made to determine the structural requirements for natural ligands for Va19 NKT cells. | ỊFEBS Journal Glycolipids with nonreducing end a-mannosyl residues that have the potential to activate invariant Va19 NKT cells Michio Shimamura1 Yi-Ying Huang1 Naoki Okamoto1 Yutaka Watanabe2 Yoshiko Murakami3 Taroh Kinoshita3 Yoshio Hirabayashi4 Chikara Murakata4 Yukishige Ito4 and Tomoya Ogawa4 1 DevelopmentalImmunology Unit Mitsubishi Kagaku Institute of Life Sciences Machida Japan 2 Faculty of Engineering Ehime University Matsuyama Japan 3 Research Institute for MicrobialDiseases Osaka University Suita Japan 4 Riken The Institute of Physicaland ChemicalResearch Wakou Japan Keywords glycolipid immune response invariant TcR a MHC class Ib NKTcell Correspondence M. Shimamura 11 Minamiooya Machida Tokyo 194-8511 Japan Fax 81 42 724 6317 Tel 81 42 724 6348 E-mail michio@ Received 26 January 2007 revised 4 April 2007 accepted 5 April 2007 doi We have previously demonstrated that a-mannosyl ceramide and its derivatives promote immune responses of invariant Va19-Ja33 T cell receptor TCR a T cells Va19 NKT cells . In this study attempts were made to determine the structural requirements for natural ligands for Va19 NKT cells. Naturally occurring and synthetic glycolipids were analyzed for their ability to stimulate the cells prepared from invariant Va19-Ja33 TCR transgenic mice in which development of Va19 NKT cells is facilitated. As a result a-mannosyl phosphatidylinositols such as 2 6-di-a-mannosyl phosphatidylinositol and a-mannosyl-4a-glucosaminyl-6-phosphatidylinositol a-Man-GlcNH2-PtdIns as well as a-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 a-mannosyl residues are suggested to be potent antigens for Va19 NKT cells. Next a series of invariant Va19-Ja33 TCR hybridomas each with variations in the sequence of the Va-Ja junction and the TCR b chain were tested for