Quantitative constraints on the scope of negative selection.

Maturing T cells with a high affinity for self-antigens presented in the thymus are deleted in the process of negative selection. Although the expression of various "tissue-specific" antigens has been described in the thymus, it is still controversial what fraction of all self-antigens induces tolerance by this mechanism. We demonstrate that the limited duration of the negative selection phase imposes a constraint on the number of self-peptides that can be reliably selected against. The analysis supports the theory that negative selection is confined to the subset of peptides produced by dendritic cells.