Based on the concept that E-specific B cells can internalize whole virus particles, they can receive help through the interaction with specific CD4 T cells not only through the presentation of peptides derived from E, but also from C. Such intra-particle help mechanisms have been demonstrated in studies with hepatitis B (34) and influenza (35, 36) and were identified as important determinant of improved Ab responses against HIV (37). The gene discussed is CD4; the disease is hepatitis B virus infection.