UMass Chan Affiliations
Department of PathologyDocument Type
Journal ArticlePublication Date
2004-02-24Keywords
AnimalsAntigen Presentation
Cloning, Molecular
Cross-Priming
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Immunoglobulin G
Mice
Mice, Inbred Strains
Ovalbumin
Rabbits
Recombinant Proteins
Subcellular Fractions
T-Lymphocytes, Cytotoxic
Transfection
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Cross-priming is essential for generating cytotoxic T lymphocytes to viral, tumor, and tissue antigens that are expressed exclusively in parenchymal cells. In this process, the antigen-bearing parenchymal cells must somehow transfer their antigens to bone marrow-derived professional antigen-presenting cells. Although intact proteins, small peptides, or peptide-heat shock protein complexes can all be acquired and presented by antigen-presenting cells, the physiologically relevant form of antigen that is actually transferred from parenchymal cells and cross-presented in vivo is unknown and controversial. To address this issue we have investigated the ability of fibroblasts stably expressing chicken ovalbumin constructs targeted to different subcellular compartments to cross-prime cytotoxic T lymphocytes. Although these transfectants generated similar amounts of the immunogenic ovalbumin peptide, their cross-priming activity differed markedly. Instead, the cells cross-priming ability correlated with their steady-state levels of ovalbumin protein and/or the physical form/location of the protein. Moreover, in subcellular fractionation experiments, the cross-priming activity colocalized with antigenic protein. In addition, depletion of intact protein antigen from these cell fractions eliminated their cross-priming activity. In contrast, the major heat shock protein candidates for cross-presentation were separable from the cell's main sources of cross-priming antigen. Therefore, cellular proteins, rather than peptides or heat shock protein/peptide complexes, are the major source of antigen that is transferred from antigen-bearing cells and cross-presented in vivo.Source
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3035-40. Epub 2004 Feb 20. Link to article on publisher's site
DOI
10.1073/pnas.0308345101Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38932PubMed ID
14978273Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.0308345101