title: A new T-cell activation mode for suboptimal doses of antigen under the full activation of T cells with different specificity.
abstract: Loss of tolerance for autoantigens is a common feature in autoimmune diseases. Bystander T-cell activation is the activation of T cells to produce functional changes through TCR-independent stimulation. Although bystander activation may be related to tolerance loss to multiple autoantigens, the activation mechanism of T cells directed to an autoantigen with limited amount is not clear. We investigated an activation mode of T cells (designated as "associator T cells") directed to a suboptimal dose of cognate antigen X in the presence of fully activated T cells (designated as "responder T cells") directed to an optimal dose of antigen Y. In in vitro coculture, the activation of associator T cells was dependent on the presentation of antigen X, and soluble factors from activated responder T cells were not sufficient. Therefore, we conclude this activation mode is different from bystander activation and named it "extended antigen priming (EAP)". T cells with EAP showed a different phenotype compared to conventionally primed cells, suggesting the unique nature of EAP. Intriguingly, EAP was dependent on the CD40-CD40L signaling pathway. Thus, the EAP model is a T-cell activation mode for suboptimal dose of antigen and presumably related to the immune response to autoantigens in autoimmune status.
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Mihoko
authors: M
authors: Shibuya
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Keishi
authors: K
authors: Fujio
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Hirofumi
authors: H
authors: Shoda
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Tomohisa
authors: T
authors: Okamura
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Akiko
authors: A
authors: Okamoto
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Shuji
authors: S
authors: Sumitomo
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors: Kazuhiko
authors: K
authors: Yamamoto
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D010641:Phenotype; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism
chemical_list: D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D023201:CD40 Ligand
keywords: Antigen specificity; Autoimmunity; Autoreactive T cells; Bystander activation; Epitope spreading