The Journal of Immunology, Vol 158, Issue 7 3155-3164, Copyright © 1997 by American Association of Immunologists

ARTICLES

Exogenously provided peptides fail to complex with intracellular class II molecules for presentation by antigen-presenting cells

T Monji and D Pious
Department of Pediatrics, University of Washington, Seattle 98195, USA.

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.

This article has been cited by other articles:

				I. Potolicchio, L. Santambrogio, and J. L. Strominger Molecular Interaction and Enzymatic Activity of Macrophage Migration Inhibitory Factor with Immunorelevant Peptides J. Biol. Chem., August 15, 2003; 278(33): 30889 - 30895. [Abstract] [Full Text] [PDF]

				A. M. Vlad, S. Muller, M. Cudic, H. Paulsen, L. Otvos Jr., F.-G. Hanisch, and O. J. Finn Complex Carbohydrates Are Not Removed During Processing of Glycoproteins by Dendritic Cells: Processing of Tumor Antigen MUC1 Glycopeptides for Presentation to Major Histocompatibility Complex Class II-restricted T Cells J. Exp. Med., December 2, 2002; 196(11): 1435 - 1446. [Abstract] [Full Text] [PDF]

				B. Wu, L. V. Elst, V. Carlier, M. G. Jacquemin, and J.-M. R. Saint-Remy The Dermatophagoides pteronyssinus Group 2 Allergen Contains a Universally Immunogenic T Cell Epitope J. Immunol., September 1, 2002; 169(5): 2430 - 2435. [Abstract] [Full Text] [PDF]

				S. Barcy and L. Corey Herpes Simplex Inhibits the Capacity of Lymphoblastoid B Cell Lines to Stimulate CD4+ T Cells J. Immunol., May 15, 2001; 166(10): 6242 - 6249. [Abstract] [Full Text] [PDF]

				M. A. Haque, J. W. Hawes, and J. S. Blum Cysteinylation of MHC Class II Ligands: Peptide Endocytosis and Reduction Within APC Influences T Cell Recognition J. Immunol., April 1, 2001; 166(7): 4543 - 4551. [Abstract] [Full Text] [PDF]

				N. S. Patil, F. C. Hall, S. Drover, D. R. Spurrell, E. Bos, A. P. Cope, G. Sonderstrup, and E. D. Mellins Autoantigenic HCgp39 Epitopes Are Presented by the HLA-DM-Dependent Presentation Pathway in Human B Cells J. Immunol., January 1, 2001; 166(1): 33 - 41. [Abstract] [Full Text] [PDF]

				N. Pimtanothai, M. Parra, A. H. Johnson, C. S. David, and C. Katovich Hurley Assessing the Binding of Four Plasmodium falciparum T Helper Cell Epitopes to HLA-DQ and Induction of T-Cell Responses in HLA-DQ Transgenic Mice Infect. Immun., March 1, 2000; 68(3): 1366 - 1373. [Abstract] [Full Text] [PDF]

				H.-K. Kang, J. A. Mikszta23, H. Deng, E. E. Sercarz, P. E. Jensen, and B. S. Kim Processing and Reactivity of T Cell Epitopes Containing Two Cysteine Residues from Hen Egg-White Lysozyme (HEL74-90) J. Immunol., February 15, 2000; 164(4): 1775 - 1782. [Abstract] [Full Text] [PDF]

				N. Panjwani, O. Akbari, S. Garcia, M. Brazil, and B. Stockinger The HSC73 Molecular Chaperone: Involvement in MHC Class II Antigen Presentation J. Immunol., August 15, 1999; 163(4): 1936 - 1942. [Abstract] [Full Text] [PDF]

				R. Lo-Man, J. P. M. Langeveld, P. Martineau, M. Hofnung, R. H. Meloen, and C. Leclerc Immunodominance Does Not Result from Peptide Competition for MHC Class II Presentation J. Immunol., February 15, 1998; 160(4): 1759 - 1766. [Abstract] [Full Text] [PDF]