A Single Peptide–MHC Complex Positively Selects a Diverse and Specific CD8 T Cell Repertoire

T cells are carefully calibrated in the thymus to react to invading pathogens and to ignore the self. This occurs through interactions between the T cell receptor and major histocompatibility complexes (MHCs) expressing self-peptides. A Goldilocks-like selection process is carried out whereby T cells that do not react or react too strongly to self-peptide MHCs are deleted, whereas those with interactions that are “just right” are allowed to survive. The result is T cells highly specific for a particular foreign peptide-MHC complex. Receipt of survival signals from “just-right” interactions (positive selection) and deletion of cells that are too reactive (negative selection) are spatially and temporally segregated in the thymus, and it is unclear at which stage T cells acquire their high degree of peptide-MHC specificity. By using mice expressing a single peptide-MHC complex, Wang et al. (p. [871][1]) now show that this single complex is sufficient for selection of a CD8+ T cell repertoire with a broad range of specificity. Importantly, recognition of peptide MHC by these cells was highly specific, demonstrating that peptide-MHC specificity is acquired during positive selection in the thymus. [1]: /lookup/doi/10.1126/science.1177627