1. IgG Epitopes Processed and Presented by IgG+ B Cells Induce Suppression by Human Thymic-Derived Regulatory T Cells
- Author
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Hsieh, Li-En, Sidney, John, Burns, Jane C, Boyle, David L, Firestein, Gary S, Altman, Yoav, Sette, Alessandro, and Franco, Alessandra
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Autoimmune Disease ,Arthritis ,Aetiology ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Adult ,Aged ,Antigen Presentation ,Arthritis ,Rheumatoid ,Dendritic Cells ,Epitopes ,B-Lymphocyte ,Female ,Histocompatibility Antigens Class II ,Humans ,Immunoglobulin Fc Fragments ,Immunoglobulin G ,Lymphocyte Activation ,Male ,Middle Aged ,Primary Cell Culture ,T-Lymphocytes ,Regulatory ,Young Adult ,Biochemistry and cell biology - Abstract
We described a human regulatory T cell (Treg) population activated by IgG+ B cells presenting peptides of the heavy C region (Fc) via processing of the surface IgG underlying a model for B cell-Treg cooperation in the human immune regulation. Functionally, Treg inhibited the polarization of naive T cells toward a proinflammatory phenotype in both a cognate and a noncognate fashion. Their fine specificities were similar in healthy donors and patients with rheumatoid arthritis, a systemic autoimmune disease. Four immunodominant Fc peptides bound multiple HLA class II alleles and were recognized by most subjects in the two cohorts. The presentation of Fc peptides that stimulate Treg through the processing of IgG by dendritic cells (DC) occurred in myeloid DC classical DC 1 and classical DC 2. Different routes of Ag processing of the IgG impacted Treg expansion in rheumatoid arthritis patients.
- Published
- 2021