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OH treatment of tetanus toxin reduces its susceptibility to limited proteolysis with more efficient presentation to specific T cells
Authors:Martine Pernollet, Christian Villiers, Fran  oise Gabert, Christian Drouet,Maurice Colomb
Affiliation:

Département de Biologie Moléculaire et Structurale, Laboratoire d'Immunochimie, INSERM Unité 238, Grenoble, France

Abstract:
At inflammatory sites, before their processing, antigens are exposed to oxygen free radicals released by activated cells. The effect of hydroxyl radicals (OH·) on the structure of a protein antigen, tetanus toxin (TT) was investigated, as well as the consequences on processing and presentation. A chemical system composed of Fe-EDTA, ascorbate and H2O2 was used to produce physiological amounts of OH radicals. TT exposed to OH· radicals presented a marked decrease of its intrinsic fluorescence with a concomitant increase of the content of bityrosine, but no fragmentation of the protein was detected by SDS-PAGE. Processing of the modified TT was analysed, by incubating TT at acidic pH with fractions enriched in plasma membranes and lysosomes obtained from a lymphoblastoid cell line (LCL). Proteolysis of OH·-treated TT was less important than proteolysis of native TT, especially upon prolonged incubations. Oxidized TT presented by LCL cells induced a greater proliferation of three different TT specific T cell clones, compared to native TT. When proteolytic digests of TT were presented by fixed LCL cells to a homologous T cell line, the proliferative response obtained in the presence of digests of OH·-treated TT was sustained, even in the case of prolonged proteolysis, whereas the response to digests of native TT fell rapidly. The relative resistance of OH·-treated TT to proteolysis appears thus responsible for its greater presentation to specific T cells, probably by protecting epitopes.
Keywords:
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