Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens.
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.
Zhou
Delu
D
Center for Immunobiology, Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Li
Ping
P
Lin
Yinling
Y
Lott
Jeremy M
JM
Hislop
Andrew D
AD
Canaday
David H
DH
Brutkiewicz
Randy R
RR
Blum
Janice S
JS
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
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