Inhibition of specific T-cell activation by monosaccharides is through their reactivity as aldehydes.
The effect of monosaccharides on the inductive interaction between antigen-presenting cells and T cells was investigated in a human system. Some monosaccharides, but not others, were found to inhibit antigen-specific T-cell activation. Responses to mitogen were unaffected. In order for inhibition to occur, a high concentration (approximately 50 mM) of monosaccharide was necessary. The role of monosaccharide aldehyde groups in inhibition was investigated using the alpha-methyl pyranoside and the alditol forms of inhibitory monosaccharides. Unlike the native monosaccharides, these molecular configurations possess the ring structure and the open chain structure respectively but do not contain aldehydes. Together they represent all the molecular characteristics of both forms of the monosaccharide except the possession of aldehyde groups. These two molecular species produced no significant inhibition. Modified forms of the sugar moiety of ribofuranosidoadenine (adenosine) were also tested. The periodate oxidized form of the molecule in which the ribose bears two aldehyde groups, was a potent inhibitor of antigen-induced T-cell activation whereas periodate-oxidized, borohydride-reduced ribofuranosidoadenine, in which the ribose aldehydes are converted to alcohols, produced no inhibition. The former was shown to form Schiff bases with ligands on peripheral blood mononuclear cells (PBMC) as predicted whereas the latter did not. Periodate oxidized dextran, but not native dextran, was also inhibitory. Together these data show that inhibition of T-cell activation by sugars requires reactive aldehydes and this is consistent with the Schiff base model of specific antigen-presenting cell (APC)-T cell inductive interaction in which exogenous aldehydes and other carbonyl donors prevent the necessary formation of Schiff bases between cellular ligands.
Rhodes
J
J
Department of Experimental Immunobiology, Wellcome Biotech, Beckenham, U.K.
Zheng
B
B
Lifely
M R
MR
D000447:Aldehydes / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D009005:Monosaccharides / Q000737:chemistry / Q000494:pharmacology*; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D000447:Aldehydes; D009005:Monosaccharides; D010835:Phytohemagglutinins; D013745:Tetanus Toxoid