Rapid extracellular degradation of synthetic class I peptides by human dendritic cells - PubMed (original) (raw)
. 1998 Oct 15;161(8):4023-32.
Affiliations
- PMID: 9780172
Rapid extracellular degradation of synthetic class I peptides by human dendritic cells
A A Amoscato et al. J Immunol. 1998.
Abstract
Dendritic cells (DCs) effectively process exogenous and endogenous Ag and present peptide in the context of both class I and class II molecules. We have demonstrated that peripheral blood DCs efficiently degrade synthetic class I peptides at their cell surface within minutes as determined by analyzing DC supernatants by HPLC. Fragments were verified as bona fide cleavage products by direct sequencing using collision-induced dissociation tandem mass spectrometry. The predominant degradative activities were 1) not secreted but associated with activity at the plasma membrane, 2) ecto-orientated, 3) not induced by peptide-specific interactions, and 4) not associated with nonspecific uptake. Sequence analysis indicated that both N- and C-terminal as well as endoproteolytic events were occurring at the cell surface. The primary exoproteolytic event was identified as CD13 or CD13-like activity through inhibition studies and could be inhibited by ubiquitin and metal-chelating agents. Endoproteolytic events could be inhibited in the presence of DTT, but the precise nature of this enzyme is still undetermined. Compared with the starting monocyte population, DCs cultured in the presence of granulocyte-macrophage CSF/IL-4 exhibited the highest degradative rate (4.3 nmol/min), followed by cultured monocytes (2.9 nmol/min) and freshly isolated monocytes (1.0 nmol/min). In addition to increased enzymatic activity, a change in substrate specificity was noted. Results are discussed with respect to APC loading, and alternatives are offered for circumventing such degradation.
Similar articles
- Breast carcinoma cell lysate-pulsed dendritic cells cross-prime MUC1-specific CD8+ T cells identified by peptide-MHC-class-I tetramers.
Bohnenkamp HR, Coleman J, Burchell JM, Taylor-Papadimitriou J, Noll T. Bohnenkamp HR, et al. Cell Immunol. 2004 Sep-Oct;231(1-2):112-25. doi: 10.1016/j.cellimm.2004.12.007. Epub 2005 Feb 8. Cell Immunol. 2004. PMID: 15919376 - Retrovirally transduced bone marrow-derived dendritic cells require CD4+ T cell help to elicit protective and therapeutic antitumor immunity.
De Veerman M, Heirman C, Van Meirvenne S, Devos S, Corthals J, Moser M, Thielemans K. De Veerman M, et al. J Immunol. 1999 Jan 1;162(1):144-51. J Immunol. 1999. PMID: 9886380 - Early activation markers of human peripheral dendritic cells.
Hellman P, Eriksson H. Hellman P, et al. Hum Immunol. 2007 May;68(5):324-33. doi: 10.1016/j.humimm.2007.01.018. Epub 2007 Feb 20. Hum Immunol. 2007. PMID: 17462499 - Generation of CMRF-44+ monocyte-derived dendritic cells: insights into phenotype and function.
Vuckovic S, Fearnley DB, Mannering SI, Dekker J, Whyte LF, Hart DN. Vuckovic S, et al. Exp Hematol. 1998 Dec;26(13):1255-64. Exp Hematol. 1998. PMID: 9845382
Cited by
- Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb).
Mendoza-Salazar I, Fragozo A, González-Martínez AP, Trejo-Martínez I, Arreola R, Pavón L, Almagro JC, Vallejo-Castillo L, Aguilar-Alonso FA, Pérez-Tapia SM. Mendoza-Salazar I, et al. Pharmaceuticals (Basel). 2024 Jan 31;17(2):185. doi: 10.3390/ph17020185. Pharmaceuticals (Basel). 2024. PMID: 38399400 Free PMC article. Review. - Peptides for Vaccine Development.
Hamley IW. Hamley IW. ACS Appl Bio Mater. 2022 Mar 21;5(3):905-944. doi: 10.1021/acsabm.1c01238. Epub 2022 Feb 23. ACS Appl Bio Mater. 2022. PMID: 35195008 Free PMC article. Review. - Bioengineering Strategies for Developing Vaccines against Respiratory Viral Diseases.
Iyer S, Yadav R, Agarwal S, Tripathi S, Agarwal R. Iyer S, et al. Clin Microbiol Rev. 2022 Jan 19;35(1):e0012321. doi: 10.1128/CMR.00123-21. Epub 2021 Nov 17. Clin Microbiol Rev. 2022. PMID: 34788128 Free PMC article. Review. - Systemic antiviral immunization by virus-mimicking nanoparticles-decorated erythrocytes.
Wang L, Wang X, Yang F, Liu Y, Meng L, Pang Y, Zhang M, Chen F, Pan C, Lin S, Zhu X, Leong KW, Liu J. Wang L, et al. Nano Today. 2021 Oct;40:101280. doi: 10.1016/j.nantod.2021.101280. Epub 2021 Sep 4. Nano Today. 2021. PMID: 34512795 Free PMC article. - CD13/Aminopeptidase N Is a Potential Therapeutic Target for Inflammatory Disorders.
Lu C, Amin MA, Fox DA. Lu C, et al. J Immunol. 2020 Jan 1;204(1):3-11. doi: 10.4049/jimmunol.1900868. J Immunol. 2020. PMID: 31848300 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Miscellaneous