This article is a tribute to Eli Sercarz and draws on his proposal of a hierarchical order of T-cell determinants in antigen presentation and T-cell activation. Here I revisit the concept of dominance and crypticity in the context of lymphocyte cooperation in the generation of the adaptive immune response, with emphasis on Th-Th cooperation. The remarks made in this article serve as a basis for a reassessment of the unresponsiveness of self-tumor antigens and how to leverage cryptic T-cell determinants operationally to generate antitumor T-cell immunity.