title: Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens.
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.
authors.affiliation: Center for Immunobiology, Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Delu
authors.initials: D
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yinling
authors.initials: Y
authors.lastname: Lin
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Lott
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hislop
authors.forename: David H
authors.initials: DH
authors.lastname: Canaday
authors.forename: Randy R
authors.initials: RR
authors.lastname: Brutkiewicz
authors.forename: Janice S
authors.initials: JS
authors.lastname: Blum
mesh_terms: D018528:ATP-Binding Cassette Transporters; D017951:Antigen Presentation; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000276:immunology; D018274:Electroporation; D011992:Endosomes / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D051907:Lysosomal Membrane Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C477327:transporter associated with antigen processing (TAP); D005968:Glutamate Decarboxylase