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

Immunity. 2005 May;22(5):571-81. doi: 10.1016/j.immuni.2005.03.009.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters
  • Antigen Presentation*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line
  • Cytoplasm / immunology
  • Electroporation
  • Endosomes / immunology
  • Glutamate Decarboxylase / immunology
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • In Vitro Techniques
  • Lysosome-Associated Membrane Glycoproteins
  • Lysosomes / immunology
  • Peptide Fragments / immunology
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transfection

Substances

  • ATP-Binding Cassette Transporters
  • Antigens, CD
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Lysosome-Associated Membrane Glycoproteins
  • Peptide Fragments
  • Recombinant Proteins
  • transporter associated with antigen processing (TAP)
  • Glutamate Decarboxylase