Invariant chain modulates HLA class II protein recycling and peptide presentation in nonprofessional antigen presenting cells

Azizul Haque, Laela M. Hajiaghamohseni, Ping Li, Katherine Toomy, Janice S. Blum

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

The expression of MHC class II molecules and the invariant chain (Ii) chaperone, is coordinately regulated in professional antigen presenting cells (APC). Ii facilitates class II subunit folding as well as transit and retention in mature endosomal compartments rich in antigenic peptides in these APC. Yet, in nonprofessional APC such as tumors, fibroblasts and endocrine tissues, the expression of class II subunits and Ii may be uncoupled. Studies of nonprofessional APC indicate class II molecules access antigenic peptides by distinct, but poorly defined pathways in the absence of Ii. Here, investigations demonstrate that nonprofessional APC such as human fibroblasts lacking Ii internalize antigenic peptides prior to the binding of these ligands to recycling class II molecules. By contrast, fibroblast lines expressing Ii favor exogenous peptides binding directly to cell surface class II molecules without a need for ligand internalization. Endocytosis of class II molecules was enhanced in cells lacking Ii compared with Ii-expressing APC. These results suggest enhanced reliance on the endocytic recycling pathway for functional class II presentation in nonprofessional APC.

Original languageEnglish (US)
Pages (from-to)20-29
Number of pages10
JournalCellular Immunology
Volume249
Issue number1
DOIs
StatePublished - Sep 1 2007

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Keywords

  • Antigen presenting cells (APC)
  • CD4+ T cell recognition
  • Endocytosis and recycling
  • Fibroblasts
  • HLA class II
  • Invariant chain (Ii)
  • Peptide binding
  • Peptide presentation

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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