Structural studies of Vgamma2Vdelta2 T cell phosphoantigens.
Human gammadelta T cells containing the Vgamma2Vdelta2 (Vgamma9Vdelta2) 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 gammadelta 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.
Zhang
Yonghui
Y
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Song
Yongcheng
Y
Yin
Fenglin
F
Broderick
Erin
E
Siegel
Kathryn
K
Goddard
Amanda
A
Nieves
Edward
E
Pasa-Tolic
Ljiljana
L
Tanaka
Yoshimasa
Y
Wang
Hong
H
Morita
Craig T
CT
Oldfield
Eric
E
D000942:Antigens, Bacterial / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009161:Mycobacterium / Q000276:immunology; D010755:Organophosphates / Q000737:chemistry* / Q000276:immunology*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
C400749:3-formyl-1-butyl pyrophosphate; C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D000942:Antigens, Bacterial; D010755:Organophosphates; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014614:Vaccines, Synthetic