TAP-Independent MHC Class I Presentation

The predominant pathway leading to Major Histocompatibility Complex (MHC) class I presentation of endogenous peptides includes their transport via Transporter associated with Antigen Processing (TAP) molecules. From TAP deficient cells it is, however, known that the ligands of some MHC class I alleles can be presented in a TAP-independent fashion. Professional Antigen Presenting Cells (APCs), which present exogenously acquired peptides, also apply both TAP-dependent and -independent pathways for their MHC class I presentation. TAP-independent pathways for MHC class I presentation of endogenous peptides is interesting for several reasons: Firstly, many virus and tumours specifically inhibit TAP function to avoid immune detection. Secondly, TAP has been shown to be a limiting factor in antigen presentation and it is therefore likely that other "less crowded" routes are more efficient. Thirdly, since the ligands of some MHC class I molecules are poor TAP substrates they need other means of gaining access to loadable MHC class I molecules. When designing epitope-based vaccines, it may therefore prove essential to take the TAP-independent pathways into consideration. In this review we focus on the many different intracellular pathways that have been suggested to lead to TAP-independent MHC class I presentation of endogenous peptides.