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 Brutkiewicz, Janice Blum

Research output: Contribution to journalArticle

203 Citations (Scopus)

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

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Antigen Presentation
HSC70 Heat-Shock Proteins
Lysosome-Associated Membrane Glycoproteins
Protein Isoforms
Autoantigens
Antigen-Presenting Cells
Epitopes
Peptides
Autophagy
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Zhou, D., Li, P., Lin, Y., Lott, J. M., Hislop, A. D., Canaday, D. H., ... Blum, J. (2005). Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity, 22(5), 571-581. https://doi.org/10.1016/j.immuni.2005.03.009

Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. / Zhou, Delu; Li, Ping; Lin, Yinling; Lott, Jeremy M.; Hislop, Andrew D.; Canaday, David H.; Brutkiewicz, Randy; Blum, Janice.

In: Immunity, Vol. 22, No. 5, 05.2005, p. 571-581.

Research output: Contribution to journalArticle

Zhou, D, Li, P, Lin, Y, Lott, JM, Hislop, AD, Canaday, DH, Brutkiewicz, R & Blum, J 2005, 'Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens', Immunity, vol. 22, no. 5, pp. 571-581. https://doi.org/10.1016/j.immuni.2005.03.009
Zhou D, Li P, Lin Y, Lott JM, Hislop AD, Canaday DH et al. Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity. 2005 May;22(5):571-581. https://doi.org/10.1016/j.immuni.2005.03.009
Zhou, Delu ; Li, Ping ; Lin, Yinling ; Lott, Jeremy M. ; Hislop, Andrew D. ; Canaday, David H. ; Brutkiewicz, Randy ; Blum, Janice. / Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. In: Immunity. 2005 ; Vol. 22, No. 5. pp. 571-581.
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