Major histocompatibility complex class I-restricted presentation of protein antigens without prior intracellular processing.
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.
Diegel
M L
ML
Dendreon Corporation, Seattle, WA 98121, USA.
Chen
F
F
Laus
R
R
Graddis
T J
TJ
Vidovic
D
D
D000818:Animals; D017951:Antigen Presentation; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D015395:Histocompatibility Antigens Class I; D010047:Ovalbumin; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins