The number of potential antigens exceeds the number of T cells in the immune system and the ability to recognize multiple ligands is required to mount at least a few responses to all potential pathogens [8] . Here, we demonstrate that the number of expected T cell ligands is not necessarily reduced by restricting T cell recognition to cover only similar peptides: it is still possible for a T cell to recognize 10 5 210 6 peptides. These estimates of the complexity of CTL recognition are well within the bounds of earlier estimates [8] . In summary, the results presented here quantify, to our knowledge for the first time, that the basis of T cell recognition is amino acid similarity, defined in terms of biochemical properties of amino acid side chains.