Exogenously provided peptides fail to complex with intracellular class II molecules for presentation by antigen-presenting cells.
Exogenously supplied antigenic peptides can bind to and be presented by cell surface class II molecules of APCs without prior processing. However, it has been unclear whether peptide Ags exogenously supplied to APCs can also form complexes with nascent intracellular class II molecules that contribute to Ag presentation. We found that exogenously provided peptide Ags, unlike whole protein Ags, are presented as efficiently by fixed as by unfixed B lymphoblastoid APCs, suggesting that intracellular processes do not contribute to the presentation of exogenously supplied peptides by unfixed APCs. Consistent with this finding, exogenously provided peptides do not bind detectably to nascent intracellular class II molecules. We studied the basis for this failure. First, as compared with whole proteins, exogenously supplied peptides accumulate very poorly intracellularly. Second, peptides are more rapidly exocytosed. The limited ability of APCs to accumulate exogenously supplied peptides intracellularly provides a likely explanation for the failure of these peptides to associate with nascent intracellular class II molecules. Exogenously supplied peptides probably never reach the intracellular vesicles in which peptide loading of class II molecules occurs. These findings have implications for the use of peptides therapeutically to block presentation of autoantigens in autoimmune disease.
Monji
T
T
Department of Pediatrics, University of Washington, Seattle 98195, USA.
Pious
D
D
D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D010450:Endopeptidases; D005089:Exocytosis / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D013745:Tetanus Toxoid / Q000138:chemical synthesis / Q000378:metabolism; D014373:Tuberculin / Q000378:metabolism
D006514:Hepatitis B Surface Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D013745:Tetanus Toxoid; D014373:Tuberculin; D010450:Endopeptidases