Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways Journal Article
| Authors: | Castellino, F.; Boucher, P. E.; Eichelberg, K.; Mayhew, M.; Rothman, J. E.; Houghton, A. N.; Germain, R. N. |
| Article Title: | Receptor-mediated uptake of antigen/heat shock protein complexes results in major histocompatibility complex class I antigen presentation via two distinct processing pathways |
| Abstract: | Heat shock proteins (HSPs) derived from tumors or virally infected cells can stimulate antigen-specific CD8+ T cell responses in vitro and in vivo. Although this antigenicity is known to arise from HSP-associated peptides presented to the immune system by major histocompatibility complex (MHC) class I molecules, the cell biology underlying this presentation process remains poorly understood. Here we show that HSP 70 binds to the surface of antigen presenting cells by a mechanism with the characteristics of a saturable receptor system. After this membrane interaction, processing and MHC class I presentation of the HSP-associated antigen can occur via either a cytosolic (transporter associated with antigen processing [TAP] and proteasome-dependent) or an endosomal (TAP and proteasome-independent) route, with the preferred pathway determined by the sequence context of the optimal antigenic peptide within the HSP-associated material. These findings not only characterize two highly efficient, specific pathways leading to the conversion of HSP-associated antigens into ligands for CD8+ T cells, they also imply the existence of a mechanism for receptor-facilitated transmembrane transport of HSP or HSP-associated ligands from the plasma membrane or lumen of endosomes into the cytosol. |
| Keywords: | signal transduction; controlled study; nonhuman; t cells; t lymphocyte; animal cell; mouse; animals; mice; cells, cultured; proteasome endopeptidase complex; mice, inbred c57bl; antigen presentation; immunology; immune response; amino acid sequence; molecular sequence data; peptides; cattle; immunostimulation; macrophages; multienzyme complexes; membrane transport; antigen presenting cell; vaccines; hsp70 heat-shock proteins; major histocompatibility antigen class 1; endosome; mice, inbred c3h; egg proteins; heat shock protein; cysteine endopeptidases; ovalbumin; antigenicity; h-2 antigens; priority journal; article; macrophage-1 antigen; macrophages, peritoneal |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 191 |
| Issue: | 11 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2000-06-05 |
| Start Page: | 1957 |
| End Page: | 1964 |
| Language: | English |
| DOI: | 10.1084/jem.191.11.1957 |
| PUBMED: | 10839810 |
| PROVIDER: | scopus |
| PMCID: | PMC2213527 |
| DOI/URL: | |
| Notes: | Export Date: 18 November 2015 -- Source: Scopus |
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