Uptake and presentation of peptides
Various experimental and clinical studies have demonstrated that short allergen/autoantigen-derived T-cell-epitope peptides are capable of improving allergy and autoimmune diseases. However, uptake and presentation of short peptides by APC is insufficient.
The preferred way of APC to present peptides is uptake by endocytosis with subsequent intracellular binding to MHC molecules (see pathway 1a-c). Alternatively, it has been shown that extracellular replacement of MHC-bound peptides is possible (see pathway 2). Furthermore, binding of extracellular peptides to surface-exposed peptide-free MHC molecules has been described.
However, all of these presentation mechanisms are not efficient. Endocytotic uptake of small peptides by APC is poor, surface-attached proteases interfere with the extracellular replacement of MHC-bound peptides, and peptide-free MHC molecules on the cellular surface are rare.