A large fraction of HLA class I ligands are proteasome-generated spliced peptides

New players in the repertoire Antigen-presenting cells, such as macrophages and dendritic cells, activate immunological T cells by presenting them with antigens bound by major histocompatibility complexes (MHCs). The proteasome typically processes these antigens, which include peptides derived from both self and microbial origins. Liepe et al. now report that, surprisingly, a large fraction of peptides bound to class I MHC on multiple human cell types are spliced together by the proteasome from two different fragments of the same protein. Such merged peptides might turn out to be useful in vaccine or cancer immunotherapy development. Science , this issue p. 354