Constitutive competition by self proteins for antigen presentation can be overcome by receptor-enhanced uptake

R. G. Lorenz, J. S. Blum, P. M. Allen

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Th cells recognize a bimolecular ligand composed of a self Ia molecule and a fragment of foreign Ag that has been processed by an APC. The effect of self proteins on the processing and presentation of foreign Ag was examined in order to ascertain the mechanisms for competition between foreign and self Ag. How this competition can be overcome to allow an efficient immune response was also examined. Normal mouse serum proteins (NMS) compete for the processing and presentation of the foreign Ag bovine RNase by APC. This competition could have occurred at any of three levels in the APC: 1) Ag uptake, 2) Ag processing, or 3) the binding of Ag to an Ia molecule. No competition for either the uptake or the processing of RNase by self proteins could be demonstrated. However, self peptides do compete with foreign Ag by binding directly to Ia molecules, as has been shown previously. Thus, the observed inhibition by NMS of Ag presentation occurred because of competition for binding to the Ia molecule. We hypothesized that during the generation of an immune response this competition is overcome by enhanced uptake of foreign Ag. To test this, we compared the ability of NMS to compete for the presentation of RNase when it entered the APC via fluid-phase pinocytosis or through receptor-mediated uptake via the mannose receptor. When the RNase entered the APC through the mannose receptor, the ability of NMS to compete was dramatically reduced. Thus, self proteins constitutively compete for the presentation of foreign Ag at the level of binding to an Ia molecule, and this competition can be overcome by receptor-mediated uptake of the Ag.

Original languageEnglish (US)
Pages (from-to)1600-1606
Number of pages7
JournalJournal of Immunology
Volume144
Issue number5
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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