Synthesis of sulfated galactocerebrosides from an orthogonal beta-D-galactosylceramide scaffold for the study of CD1-antigen interactions.
CD1a protein binds sulfatide (3-O-sulfo-beta-D-galactosylceramide) to form an antigen complex that interacts with T cell receptors and activates T cells. To assess the role of the position of the sulfate in T cell activation, the synthesis of three beta-D-galactosylceramides, variously bearing a sulfate at position 2, 4, or 6 of galactose, has been planned and carried out. The compounds were synthesized by an orthogonal sulfation strategy from a common beta-D-galactosylceramide scaffold, which was in turn obtained through an efficient glycosylation reaction between a fully orthogonally protected galactosyl imidate and 3-O-benzoylazidosphingosine. Immunological evaluation of the three sulfated compounds in CD1a-mediated T cell activation, in comparison with natural sulfatide, provided evidence of the influence of the sulfate position in the recognition event between the antigen, the CD1 protein and the T cell receptor.
Compostella
Federica
F
Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano, Via Saldini 50, 20133-Milan, Italy. federica.compostella@unimi.it
Ronchi
Silvia
S
Panza
Luigi
L
Mariotti
Sabrina
S
Mori
Lucia
L
De Libero
Gennaro
G
Ronchetti
Fiamma
F
D018949:Antigens, CD1 / Q000276:immunology*; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000737:chemistry*; D006801:Humans; D008213:Lymphocyte Activation; D013433:Sulfoglycosphingolipids / Q000737:chemistry; D013463:Sulfuric Acid Esters / Q000138:chemical synthesis / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology
D018949:Antigens, CD1; C419393:CD1a antigen; D005699:Galactosylceramides; D013433:Sulfoglycosphingolipids; D013463:Sulfuric Acid Esters