The T cell is central to the immune system response to foreign antigens, and understanding the mechanism of T cell response to antigen is crucial for vaccine development. Short subpeptides of foreign antigen can prime the T cells to respond to the whole antigen, in some cases as well as or better than immunization with the whole antigen itself. Antigenic sites located first in the murine model are also antigenic in the human, suggesting that the structural features of antigenic sites are species-independent. The amphipathic helix hypothesis has proven useful in developing an algorithm that has successfully located immunodominant sites in important proteins, thus reducing substantially the experimental time and effort required to locate those sites. Other algorithms have also been used successfully, but in all cases there are proven T-cell sites not accounted for by the algorithm. A data base showing T-cell response to collections of peptides uniformly distributed along protein antigens would be very useful in subsequent efforts to characterize the physical and chemical properties of T-cell antigenic sites.