Peptides Derived from α-Tubulin Induce Functional T Regulatory Cells

Regulatory T (Treg) cells are essential for maintaining self-tolerance and regulating immune responses. In this study, we report the identification of Treg cell epitopes in human α-tubulin that were capable of enhancing IL-10-producing Foxp3+ Treg cells and LAG-3+CD49b+FoxP3− Tr1 cells in vitro, using human peripheral blood mononuclear cells. Similarly, we also demonstrate that a peptide pool containing the identified Treg cell epitopes (αTBL pool) suppressed the T cell responses elicited by HLA class I- and class II-restricted T cell epitopes. Moreover, stimulation of naive CD4+ T cells with autologous monocyte-derived dendritic cells in the presence of the αTBL pool promoted the differentiation of functional FoxP3+ Treg cells, which suppressed the proliferation of CD3/CD28-activated T cells. Finally, we show that one of the identified epitopes, identical between human and mouse, also stimulated FoxP3+ Treg cells in splenocytes isolated from C57BL/6 mice. Considering the elevated expression of α-tubulin in all cell types, the presence of Treg cell epitopes in this protein may facilitate a broad mechanism of immune regulation. Moreover, α-tubulin Treg cell epitopes may prove useful in creating novel treatments for conditions marked by excessive or misdirected immune responses.