Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens

Delu Zhou, Ping Li, Yinling Lin, Jeremy M. Lott, Andrew D. Hislop, David H. Canaday, Randy R. Brutkiewicz, Janice S. Blum

Research output: Contribution to journalArticle

213 Scopus citations

Abstract

Extracellular antigens are internalized and processed before binding MHC class II molecules within endosomal and lysosomal compartments of professional antigen presenting cells (APC) for subsequent presentation to T cells. Yet select cytoplasmic peptides derived from autoantigens also intersect and bind class II molecules via an unknown mechanism. In human B lymphoblasts, inhibition of the peptide transporter associated with antigen processing (TAP) failed to alter class II-restricted cytoplasmic epitope presentation. By contrast, decreased display of cytoplasmic epitopes via class II molecules was observed in cells with diminished expression of the lysosome-associated membrane protein-2 (Lamp-2). Overexpression of Lamp-2 isoform A (Lamp-2a), an established component of chaperone-mediated autophagy, enhanced cytoplasmic autoantigen presentation. Manipulating APC expression of heat shock cognate protein 70 (hsc70), a cofactor for Lamp-2a, also altered cytoplasmic class II peptide presentation. These results demonstrate a novel role for the lysosomal Lamp-2a-hsc70 complex in promoting immunological recognition and antigen presentation.

Original languageEnglish (US)
Pages (from-to)571-581
Number of pages11
JournalImmunity
Volume22
Issue number5
DOIs
StatePublished - May 1 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens'. Together they form a unique fingerprint.

  • Cite this