Treg cell epitopes from α -tubulin: discovery and immunomodulatory features

Regulatory T (Treg) cells are pivotal in maintaining self-tolerance and controlling immune responses. In this study, we investigated potential Treg cell epitopes in human α-tubulin that were selected in silico for their promiscuous binding to class II human leukocyte antigens and full identity with antigens from enteric nematodes present in excretory-secretory products. We identified five Treg cell epitopes in α-tubulin that were capable of stimulating and expanding IL-10 and TGF-β-producing Foxp3 ⁺ Treg cells in peripheral blood mononuclear cells. We also proved that a peptide pool containing the identified Treg cell epitopes (αTBL pool) suppressed the T cell responses elicited by different stimuli, including LPS, and class I and class II restricted T cell epitopes, as determined by intracellular cytokine staining assays. Similarly, this same peptide pool was able to suppress T cell responses in mixed lymphocyte reactions. Finally, we found that stimulation of naive CD4 ⁺ T cells with autologous monocyte-derived dendritic cells in the presence of the αTBL pool promoted the differentiation of functional CD4 ⁺ CD25 ^high FoxP3 ⁺ T cells capable of suppressing the proliferation of CD3/CD28-activated T cells. α-tubulin Treg cell epitopes could be useful for treating autoimmune and chronic inflammatory diseases by inducing Treg cells and, given the ubiquitous and copious expression of α-tubulin, enable a general mechanism of immune homeostasis.