Induction of promotive rather than suppressive immune responses from a novel NKT cell repertoire Vα19 NKT cell with α-mannosyl ceramide analogues consisting of the immunosuppressant ISP-I as the sphingosine unit

A 2-substituted 2-aminopropane-1,3-diol or 2-aminoethanol is the minimum structure required for the immunosuppressive activity of ISP-I, an antibiotic isolated from the culture broth of Isaria sinclairil. A series of α-mannosyl ceramide (α-ManCer) analogues was derived from 2-substituted 2-aminopropane-1,3-diols or 2-aminoethanols in place of sphingosine. The newly synthesized glycosides were evaluated for their effects on immune responses. In contrast to the immunosuppressive activity of the precursors, the α-ManCer analogues induced immunopromotive responses from invariant Vα19-Jα26 transgenic mouse lymphocytes more effectively than the original α-ManCer. Collectively, it is strongly suggested that the 2-substituted 2-aminopropane-1,3-diols and 2-aminoethanols mimic sphingosine in the α-ManCer analogues so that they potentially acquire specific antigenicity toward Vα19 NKT cell, a novel NKT cell subset.