Basic Science
Abstract # 1583: Febrile Temperatures Enhance Antigen Processing of Type II Collagen for Presentation to CD4 T Cells
Authors: Alexei von Delwig, Amy J. Wilson, Daniel M. Altman, Rikard Holmdahl, Clifford V. Harding, Norman McKie1, John D. Isaacs1, Jeremy H. Lakey1, John H. Robinson. University of Newcastle, Newcastle upon Tyne, United Kingdom; Human Disease Immunogenetics Group, Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom; Section for Medical Inflammation Research, Lund University, Lund, Sweden; Department of Pathology, Case Western Reserve University, Cleveland, OH
Objective: There has been some data in recent years that demonstrated physiologic temperature dependent unfolding of fibrillar collagen monomers. Since type II collagen is an RA candidate autoantigen, and can induce arthritis in mice, the authors investigated the relative immunogenicity of both intact collagen and on antigen presentation in a transgenic model.
Methods: The secondary structure of collagen incubated at different temperatures (all within the human febrile physiologic range) was assessed by circular dichroism. A Type II collagen epitope-specific T cell line was used to assess antigen presentation and processing using collagens incubated at different temperatures, and immunogenicity of these molecules was probed in vivo using T cells from mice immunized with the varying temperature-incubated molecules used in the above experiments.
Results: Type II collagen became irreversibly denatured at a temperature of nearly 42 degrees, and when this occurred became more efficiently processed by macrophages and presented with more rapid kinetics than the form incubated at lower temperatures. The collagens incubated at 41 degrees were the most highly immunogenic in vivo as well as measured by T cell proliferation assays.
Significance: Although this study is highly contrived and of questionable immediate significance to the pathogenesis of RA, the authors’ concept that the fever response itself, and not the accompanying cytokine milieu, might be involved in antigen selection and processing is an intriguing one deserving further study. If found to be true in a more general way, then the medical community would certainly look at anti-pyretic therapy in patients with RA and other autoimmune diseases in a whole new way.
