Cut and trim: generating MHC class I peptide ligands

Progress in understanding how peptide ligands are generated for MHC class I molecules took several interesting leaps and twists in the past year. Two independent lines of evidence suggest that most peptides are generated by p roteasomal digestion of nascent proteins. The amino-terminally extended cyt osolic precursors of an antigenic peptide were identified, bound to a myste rious carrier protein. Knowledge about the role of immunoproteasomes in ant igen processing was fortified, cellular locales specialized for proteasomal degradation (and possibly antigenic-peptide production) were discovered an d novel cytosolic proteases potentially involved in generating and trimming antigenic peptides were identified. The field is poised for quantitative a nalysis of the various pathways that contribute to the pool of peptides pre sented to the immune system by MHC class I molecules.