Here, we first reported that immunodomination occurred between serotype-specific CD4+ T-cell epitopes after immunization with a tetravalent MV-vectored dengue vaccine, and the DENV-3 epitope became an immunodominant epitope limiting the immune responses to other serotype epitopes; however, the subdominant DENV-2-specific CD4+ T-cell epitope switched to a dominant epitope after DENV-2 challenge. Here, CD4 is linked to dengue disease.