The reactivities of human erythrocyte autoantibodies anti-Pr2, anti-Gd, Fl and Sa with gangliosides in a chromatogram binding assay

Abstract

The thin layer chromatogram binding assay was used to study the reaction of several natural-monoclonal autoantibodies which recognize sialic acid-dependent antigens of human erythrocytes. Immunostaining of gangliosides derived from human and bovine erythrocytes was achieved with four autoantibodies designated anti-Pr2, anti-Gd, Sa and Fl, each of which has a different haemagglutination pattern with untreated and proteinase-treated erythrocytes and with cells of I and i antigen types. From the chromatogram binding patterns of anti-Pr2 with gangliosides of the neolacto and the ganglio series, it is deduced that this antibody reacts best with N-acetylneuraminic acid when it is alpha 2-3- or alpha 2-6-linked to a terminal Gal(beta 1-4)Glc/GlcNAc GlcNAc sequence and to a lesser extent when it is alpha 2-3-linked to a terminal Gal(beta 1-3)GalNAc sequence or to an internal galactose and when it is alpha 2-8-linked to another, internal N-acetylneuraminic acid residue. The other three antibodies differ from anti-Pr2 in their lack of reaction with glycolipids of the ganglio series. They react with the NeuAc(alpha 2-3)Gal(beta 1-4)Glc/GlcNAc sequence as found in GM3 and in glycolipids of the neolacto series, but show a preference for the latter, longer sequences. Thus all four antibodies react with sialylated oligosaccharides containing i type (linear) and I type (branched) neolacto backbones. Fl antibody differs from the other three in its stronger reaction with branched neolacto sequences in accordance with its stronger agglutination of erythrocytes of I rather than i type. The four antibodies show a specificity for N-acetyl- rather than N-glycolyl-neuraminic acid.

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

“…Ha1 binds to disialosyl gangliosides and to the Pr 2 antigen on red blood cells, a cross reactivity first recognized many years ago (44). The variable regions encoding Ha1 are V H 1 and V 2 family members and show clear evidence of mutation from their associated germline sequences within heavy and light chain CDRs, suggesting that this antibody has undergone antigen-driven somatic mutation.…”

α2,3-Specific Desialylation of Human Red Cells: Effect on the Autoantigens of the Pr, Sa and Sia-l1, -b1, -lb1 Series

“…In 1984, one anti-Pr 2 had been shown to react with gangliosides [4]. Because the reaction of that antibody with human RBCs was abolished by proteases, one could conclude that gangliosides do not contribute to the reaction of the anti-Pr 2 with human RBCs.…”

“…The antigens of these series, formerly termed Vo, F1, Gd, have been demonstrated to be gangliosides [4, 5]. Gangliosides contain NeuNAcα2–3Gal and/or NeuNAcα2–8NeuNAc sequences.…”

“…. sequence [4]. (2) Pr antigens resistant to α2,3-specific sialidase use groups other than α2,3NeuNAc.…”

Coexisting Anti-I and Anti-Fl/Gd Cold Agglutinins in Infections by Mycoplasma pneumoniae

“…Anti-I would then be an autoantibody directed against the backbone structure of the receptor. Figure 1 shows the structures recognized by CA of the specificities anti-I, anti-i, anti-FI, and anti-Gd [2,3,26,27], As may be seen from the figure, the complete, sialylated structures which were identified as M.pneumoniae receptors are identical with the antigens recognized by anti-FI and anti-Gd CA. The fact that, as our results show, anti-Fl/Gd CA occur together with anti-I in the majority of cases of M. pneumoniae-induced CA production, there fore, adds further support to the hypothesis that postin fectious CA are directed against the receptor of the infec tious agent [12], This hypothesis may be extended to infectious agents other than M. pneumoniae as well, since most virus receptors so far investigated are glycoproteins and glycolipids with specific oligosaccharide sequences [28][29][30]; in fact, the carbohydrate structures identified as receptors for M. pneumoniae have also been implicated as receptors for Sendai [31] and influenza [32] viruses, the latter of which has recently been reported to elicit CA of anti-I specificity [33].…”