Both helper and cytotoxic T cells see primarily a limited number of immunodominant sites on a protein. The reasons for immunodominance are many. We have explored primarily the roles of antigen processing and binding to histocompatibility molecules, as well as the structural features of the antigenic peptide. This information has led to the identification and characterization of sites stimulating helper or cytotoxic T cells specific for antigens from malaria or HIV, and ways to couple and immunize with these, that may be useful for vaccine development. We also observed a striking concordance between helper and cytotoxic T cell sites.