MHC class I-restricted presentation of maleylated protein binding to scavenger receptors

Bansal, Pratima ; Mukherjee, Paushali ; Basu, Sandip K. ; George, Anna ; Bal, Vineeta ; Rath, Satyajit (1999) MHC class I-restricted presentation of maleylated protein binding to scavenger receptors Journal of Immunology, 162 . pp. 4430-4437. ISSN 0022-1767

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Official URL: http://www.jimmunol.org/cgi/content/abstract/162/8...

Abstract

Pathways for loading exogenous protein-derived peptides on MHC class I are thought to be present mainly in monocyte-lineage cells and to involve phagocytosis- or macropinocytosis-mediated antigenic leakage into either cytosol or extracellular milieu to give peptide access to MHC class I. We show that maleylation of OVA enhanced its presentation to an OVA-specific MHC class I-restricted T cell line by both macrophages and B cells. This enhanced presentation involved uptake through receptors of scavenger receptor (SR)-like ligand specificity, was TAP-1-independent, and was inhibited by low levels (2 mM) of ammonium chloride. No peptide loading of bystander APCs by maleylated (maleyl) OVA-pulsed macrophages was detected. Demaleylated maleyl-OVA showed enhanced MHC class I-restricted presentation through receptor-mediated uptake and remained highly sensitive to 2 mM ammonium chloride. However, if receptor binding of maleyl-OVA was inhibited by maleylated BSA, the residual presentation was relatively resistant to 2 mM ammonium chloride. Maleyl-OVA directly introduced into the cytosol via osmotic lysis of pinosomes was poorly presented, confirming that receptor-mediated presentation of exogenous maleyl-OVA was unlikely to involve a cytosolic pathway. Demaleylated maleyl-OVA was well presented as a cytosolic Ag, consistent with the dependence of cytosolic processing on protein ubiquitination. Thus, receptor-specific delivery of exogenous protein Ags to APCs can result in enhanced MHC class I-restricted presentation, suggesting that the exogenous pathway of peptide loading for MHC class I may be a constitutive property dependent mainly on the quantity of Ag taken up by APCs.

Item Type:Article
Source:Copyright of this article belongs to American Association of Immunologists.
ID Code:1836
Deposited On:08 Oct 2010 12:00
Last Modified:16 May 2016 12:53

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