Circulating human rotavirus specific CD4 T cells identified with a class II tetramer express the intestinal homing receptors α4β7 and CCR9

•A DR1 restricted epitope derived from the rotavirus VP6 protein was identified.•CD4 T cells specific for this epitope were characterized using class II tetramers.•CD4 T cells specific for the rotavirus epitope but not specific for an influenza epitope expressed intestinal homing receptors.

Using a consensus epitope prediction approach, three rotavirus (RV) peptides that induce cytokine secretion by CD4 T cells from healthy volunteers were identified. The peptides were shown to bind HLA-DRB1⁎0101 and then used to generate MHC II tetramers. RV specific T cell lines specific for one of the three peptides studied were restricted by MHC class II molecules and contained T cells that bound the tetramer and secreted cytokines upon activation with the peptide. The majority of RV and Flu tetramer+ CD4 T cells in healthy volunteers expressed markers of antigen experienced T cells, but only RV specific CD4 T cells expressed intestinal homing receptors. CD4 T cells from children that received a RV vaccine, but not placebo recipients, were stained with the RV-VP6 tetramer and also expressed intestinal homing receptors. Circulating RV-specific CD4 T cells represent a unique subset that expresses intestinal homing receptors.