Human Natural Regulatory T Cells Recognize Peptides of the Heavy Constant Region of IgG with High Sequence Homology with Peptides Derived from Pathogens

Abstract

Human natural regulatory T cells (nTreg) that control the differentiation of pro-inflammatory T cells recognize the heavy constant region of immunoglobulins G (Fc). We defined 16 peptides, 15 amino acids long, out of the whole Fc sequence immunogenic in healthy donors and patients with Rheumatoid Arthritis, a systemic autoimmune disease. In Immunology it is still debated how the thymic selection of T cells that recognize “self” peptides occurs as these T cells could be potentially harmful. However, nTreg recognize “self” and are very important in controlling the immune homeostasis. Here we show by screening the Immune epitope Data Base (IEDB) that the immunodominant Fc peptides that stimulate nTreg have a very high sequence homology with “non-self” peptides derived from a variety of pathogens. These results suggest that T cells with T cell receptors that recognize “self” peptides could be rescued from the negative selection in the thymus by engaging antigenic peptides with high sequence homology and or that pathogens may inhibit the immune regulation by jeopardizing nTreg expansion by T cell receptor antagonism.