Journal
CLINICAL IMMUNOLOGY
Volume 224, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2020.108661
Keywords
Factor V (FV); Factor VIII (FVIII); Anti-drug-antibody (ADA); Immunogenicity; Hemophilia; Tolerance; Tregitope; Inhibitor; Treg; Regulatory T cell epitope
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Identification of T cell epitopes recognized by Tregs can help understand the role of thymic Tregs and induced Tregs in autoimmune diseases and allergies. The Tregitope FV621 derived from Factor V has potent immunomodulatory effects, suppressing CD4+ and CD8+ T cell responses and inhibiting immune responses in vivo and in vitro, especially when conjugated to albumin. Prospective identification tools combined with validating assays may facilitate future Tregitope discoveries.
Identification of T cell epitopes that are recognized by Tregs may elucidate the relative contributions of thymic Tregs and induced Tregs to control of autoimmune diseases and allergy. One such T regulatory cell epitope or 'Tregitope', derived from blood Factor V, is described here. Tregs responding to Tregitope FV621 are potent suppressors of CD4+ T effector responses to Tetanus Toxoid in an in vitro bystander suppression assay, strongly inhibit proliferation of effector CD8+ T cells, down-modulate CD86 and HLA DR on antigen-presenting cells, and enhance expression of granzyme B in Tregs. Tregitope FV621 also suppresses anti-OVA immune responses in vivo. The immunomodulatory effect of Tregitope FV621 is enhanced when conjugated to albumin, suggesting that the short half-life of Tregitope peptides can be prolonged. The in silico tools used to prospectively identify the FV Tregitope described here, when combined with in vitro /in vivo validating assays, may facilitate future Tregitope discoveries.
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