TY - JOUR
T1 - Structural Studies of Vγ2Vδ2 T Cell Phosphoantigens
AU - Zhang, Yonghui
AU - Song, Yongcheng
AU - Yin, Fenglin
AU - Broderick, Erin
AU - Siegel, Kathryn
AU - Goddard, Amanda
AU - Nieves, Edward
AU - Pasa-Tolic, Ljiljana
AU - Tanaka, Yoshimasa
AU - Wang, Hong
AU - Morita, Craig T.
AU - Oldfield, Eric
N1 - Funding Information:
This work was supported by the U.S. Public Health Service (NIH grants GM073216 to E.O.; AR045504 and AI057160 to C.T.M.). Y.Z. was supported by an American Heart Association, Greater Midwest Affiliate, Postdoctoral Fellowship. Y.S. is a Leukemia and Lymphoma Society Special Fellow. We are very grateful to Professor José-Luis Giner for providing HMBPP, Drs. J.-J. Fournié and M. Eberl for their helpful comments, Dr. F. Lin for recording the COSY spectrum, and John Sanders and Michael Hudock for help with data analysis. The exact mass determinations were performed at the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory.
PY - 2006/9
Y1 - 2006/9
N2 - Human γδ T cells containing the Vγ2Vδ2 (Vγ9Vδ2) T cell receptor are stimulated by a broad variety of small, phosphorus-containing antigenic molecules called phosphoantigens. The structures of several species present in both Mycobacteria (TUBags1-4) and in Escherichia coli have been reported to contain a formyl-alkyl diphosphate core. Here we report the synthesis of the lead member of the series, 3-formyl-1-butyl diphosphate. This compound has low activity for γδ T cell stimulation, unlike its highly active isomer (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate, necessitating a revision of the structure of TUBag1. Likewise, the structure of the species identified as the pentyl analog (TUBag 2) is revised to 6-phosphogluconate. These results indicate that neither TUBag1 nor the m/e 275 species proposed for TUBag2 are 3-formyl-1-alkyl diphosphates, leading to the conclusion that none of the natural phosphoantigens (TUBags1-4) possess the structures reported previously.
AB - Human γδ T cells containing the Vγ2Vδ2 (Vγ9Vδ2) T cell receptor are stimulated by a broad variety of small, phosphorus-containing antigenic molecules called phosphoantigens. The structures of several species present in both Mycobacteria (TUBags1-4) and in Escherichia coli have been reported to contain a formyl-alkyl diphosphate core. Here we report the synthesis of the lead member of the series, 3-formyl-1-butyl diphosphate. This compound has low activity for γδ T cell stimulation, unlike its highly active isomer (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate, necessitating a revision of the structure of TUBag1. Likewise, the structure of the species identified as the pentyl analog (TUBag 2) is revised to 6-phosphogluconate. These results indicate that neither TUBag1 nor the m/e 275 species proposed for TUBag2 are 3-formyl-1-alkyl diphosphates, leading to the conclusion that none of the natural phosphoantigens (TUBags1-4) possess the structures reported previously.
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U2 - 10.1016/j.chembiol.2006.08.007
DO - 10.1016/j.chembiol.2006.08.007
M3 - Article
C2 - 16984888
AN - SCOPUS:33748613776
SN - 1074-5521
VL - 13
SP - 985
EP - 992
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 9
ER -