Consistent with the findings of subdominant CD8+ T cells in other virus infections (31), the subdominant DENV-2 peptide D2-10-specific CD4+ T-cell response was recalled following DENV-2 challenge and conferred protection with high levels of IFN-γ and IL-2 production, as well as a significant increase in DENV-2-specific NT and IgG avidity. Here, CD4 is linked to viral infectious disease.