TY - JOUR
T1 - Modulation of Vα19 NKT cell immune responses by α-mannosyl ceramide derivatives consisting of a series of modified sphingosines
AU - Shimamura, Michio
AU - Huang, Yi Ying
AU - Okamoto, Naoki
AU - Suzuki, Nahoko
AU - Yasuoka, Jouji
AU - Morita, Kenji
AU - Nishiyama, Akira
AU - Amano, Yuusuke
AU - Mishina, Tadashi
PY - 2007/7
Y1 - 2007/7
N2 - We have demonstrated that analogues of α-mannosyl ceramide (α-ManCer) consisting of a series of immunosuppressive 2-aminoalcohol derivatives in place of sphingosine promote a greater immune response from mouse invariant Vα19-Jα26 (AV19-AJ33) TCR-bearing NKT (Vα19 NKT) cells than α-ManCer itself. To further characterize the immune responses of Vα19 NKT cells to the α-ManCer analogues, cytokine production by the cells was examined in detail. We found that certain α-ManCer derivatives individually induced either Th1- or Th2-dominant cytokine production in culture. The Th1- or Th2-biased immune responses of Vα19 NKT cells were dependent on MHC class I-like MR1, since they were induced by coculture with the MR1 transfectants previously loaded with the glycolipids and were inhibited in the presence of anti-MR1 antiserum. Presumably, the recognition of the α-mannosyl residue of the α-ManCer analogues by the invariant TCR is individually modulated, depending on the altered interaction with the groove of the antigen-presenting MR1. Priming of the Vα19 invariant TCR-transgenic mice in vivo with these glycolipid derivatives resulted in the induction of the Thl- or Th2-biased immune responses. Thus, these α-ManCer derivatives are likely to be useful in immunotherapy for either Th1 or Th2 excess autoimmune diseases, modulating the function of Vα19 NKT cells.
AB - We have demonstrated that analogues of α-mannosyl ceramide (α-ManCer) consisting of a series of immunosuppressive 2-aminoalcohol derivatives in place of sphingosine promote a greater immune response from mouse invariant Vα19-Jα26 (AV19-AJ33) TCR-bearing NKT (Vα19 NKT) cells than α-ManCer itself. To further characterize the immune responses of Vα19 NKT cells to the α-ManCer analogues, cytokine production by the cells was examined in detail. We found that certain α-ManCer derivatives individually induced either Th1- or Th2-dominant cytokine production in culture. The Th1- or Th2-biased immune responses of Vα19 NKT cells were dependent on MHC class I-like MR1, since they were induced by coculture with the MR1 transfectants previously loaded with the glycolipids and were inhibited in the presence of anti-MR1 antiserum. Presumably, the recognition of the α-mannosyl residue of the α-ManCer analogues by the invariant TCR is individually modulated, depending on the altered interaction with the groove of the antigen-presenting MR1. Priming of the Vα19 invariant TCR-transgenic mice in vivo with these glycolipid derivatives resulted in the induction of the Thl- or Th2-biased immune responses. Thus, these α-ManCer derivatives are likely to be useful in immunotherapy for either Th1 or Th2 excess autoimmune diseases, modulating the function of Vα19 NKT cells.
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U2 - 10.1002/eji.200636689
DO - 10.1002/eji.200636689
M3 - Article
C2 - 17559170
AN - SCOPUS:34447554385
SN - 0014-2980
VL - 37
SP - 1836
EP - 1844
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 7
ER -