PubMed · 14313505
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W A SIBLEY, J M FOLEY. 1965-03-31. INFECTION AND IMMUNIZATION IN MULTIPLE SCLEROSIS.. https://doi.org/10.1111/j.1749-6632.1965.tb20229.x
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Organ hyperacute rejection, a phenomenon occurring during discordant xenotransplantation, is due to the recognition of an oligosaccharide epitope by human xenoreactive natural antibodies. In addition to the alpha Gal(1-3)beta Gal(1-4)GlcNAc trisaccharide, a fucosylated structure, alpha Gal-Lewis X, has been shown to be recognized by the antibodies. Both the trisaccharide and the tetrasaccharide have been synthesized by chemical methods. A complete nuclear magnetic resonance characterization of the two compounds has been performed, including the measurements of two-dimensional nuclear Overhauser effect spectroscopy data. Molecular dynamics simulations were run for several ns in the presence of explicit water molecules. The combination of experimental and theoretical approaches revealed the effect of an additional fucose residue on the conformational behavior of the xenoantigen. This branched fucose strongly rigidifies the N-acetyllactosamine. The effect on the alpha Gal(1-3)Gal fragment is less marked. In the presence of fucose, the terminal alpha Gal residue can still adopt two different conformations, but the equilibrium populations are modified.
In recent years there has been significant progress in the development of attenuated Salmonella enterica serovar Typhi strains as candidate typhoid fever vaccines. In clinical trials these vaccines have been shown to be well tolerated and immunogenic. For example, the attenuated S. enterica var. Typhi strains CVD 908-htrA (aroC aroD htrA), Ty800 (phoP phoQ) and chi4073 (cya crp cdt) are all promising candidate typhoid vaccines. In addition, clinical trials have demonstrated that S. enterica var. Typhi vaccines expressing heterologous antigens, such as the tetanus toxin fragment C, can induce immunity to the expressed antigens in human volunteers. In many cases, the problems associated with expression of antigens in Salmonella have been successfully addressed and the future of Salmonella vaccine development is very promising.
The implantation of animal organs is one approach to overcoming the shortage of human donor organs for medical transplantation. Although readily available, non-primate tissues are subject to hyperacute rejection wherein human anti-Galalpha(1-3)Gal antibodies react with haptens present on the transplanted cells' surfaces. The understanding of this interaction on a molecular level will further the development of a strategy for the prevention of hyperacute rejection in xenotransplantation. The Galalpha(1-3)Gal hapten ('xenograft antigen') has been cocrystallized with the Gal-specific B(4) isolectin of Griffonia simplicifolia lectin-1. Crystals were analyzed by cryocrystallography and were found to diffract to moderately high resolution on a rotating-anode X-ray source. They belong to the P2(1)2(1)2 space group, with unit-cell parameters a = 111.0, b = 51.3, c = 76.9 A, and contain two molecules per asymmetric unit.