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

Research output: Contribution to journalArticle

Authors

  • D Zhou
  • P Li
  • Y Lin
  • JM Lott
  • RR Brutkiewicz
  • JS Blum

Colleges, School and Institutes

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.

Details

Original languageEnglish
Pages (from-to)571-581
Number of pages11
JournalImmunity
Volume22
Publication statusPublished - 1 May 2005