Major Histocompatibility Complex Class I‐Restricted Presentation of Protein Antigens without Prior Intracellular Processing

• Published in: Scandinavian journal of immunology 2003-07, Vol.58 (1), p.1-8
• Main Authors: Diegel, M. L., Chen, F., Laus, R., Graddis, T. J., Vidovic, D.
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; Female; Histocompatibility Antigens Class I - metabolism; Mice; Mice, Inbred C57BL; Ovalbumin - metabolism; Peptide Fragments - metabolism; Receptor, ErbB-2 - metabolism; Recombinant Fusion Proteins - metabolism
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1046/j.1365-3083.2003.01252.x

Proteins in their native form are incapable of stimulating antigen (Ag)‐specific T cells, which can only recognize major histocompatibility complex (MHC)‐bound peptides that have been generated by intracellular processing within antigen‐presenting cells (APCs). Here, we show that APCs can trigger MHC class I‐restricted T‐cell responses after presenting proteins without conventional intracellular processing, provided the immunostimulatory MHC class I‐binding peptide sequence is incorporated at the carboxy‐terminal position. Such MHC‐bound proteins do not stimulate T cells directly, because the contact between MHC/peptide complex and its cognate ligand is sterically hindered by the amino‐terminal bulk of the protein. Removal of the latter via an extracellular Ag proteolysis by the T‐cell‐ and/or APC‐derived enzymes is required for effective T‐cell stimulation. Our data challenge the established concept that only small peptides can bind to the MHC class I molecules.