CD4 and infection: We demonstrate that immunodominant CD4 T cell epitopes cluster within exposed strands and loops of E and in hotspots of two predicted helices of C. The immunodominance patterns generated in response to YF vaccination are very similar to those found after infection or vaccination with the distantly related TBE virus, suggesting a strong impact of structural protein features on the selection of epitopes in flavivirus CD4 T cell responses.