Low-affinity peptides and T-cell selection.

The dual requirement for T cells to recognize a particular major histocompatibility complex (MHC) antigen presenting a foreign peptide and to lack strong reactivity with a complex of the same molecule when bound to a self-peptide, is attained by thymic positive and negative selection processes, the molecular details of which are currently only partially understood. However, the discovery of the thymoproteasome and our improved understanding of the dynamics of peptide presentation permit us to suggest that the biophysical properties of the MHC:peptide class I complexes engaged in positive T-cell selection will be distinct from those involved in negative selection, hence imposing differential barriers for T cells.