Dendritic cell/macrophage precursors capture exogenous antigen for MHC class I presentation by dendritic cells.
Presentation of MHC class I antigens by professional antigen-presenting cells (APC) is an important pathway in priming cytotoxic T lymphocyte responses in vivo. This study sought to identify the nature of the professional APC responsible for indirect class I presentation by examining a special feature of professional APC, namely their ability to process exogenous forms of antigen for class I presentation. Incubation of highly purified bone marrow-derived precursor cells with chicken ovalbumin (OVA) led to the efficient presentation of the major class I-restricted OVA determinant by mature dendritic cells (DC), but not by macrophages (Mphi) derived from the precursor population. DC as well as macrophages were, however, able to mediate class II presentation of OVA, suggesting that macrophages were deficient in class I processing but not in capturing exogenous OVA. The majority of mature DC, i.e. over 80 %, generated from the precursor cells pulsed with OVA, presented the class I OVA epitope. Upon maturation, class I presentation of OVA by DC was greatly reduced, suggesting that class I processing of exogenous antigen is modulated during DC maturation in a manner similar to class II antigen processing. This study shows that bone marrow-derived DC/ME progenitors capture exogenous antigen for class I presentation, and that cells of the DC lineage can be functionally distinguished from cells of the macrophage lineage based on their ability to process exogenous antigen for class I presentation.
Mitchell
D A
DA
Department of Immunology and the Center for Genetic and Cellular Therapies, Duke University Medical Center, Durham 27710, USA.
Nair
S K
SK
Gilboa
E
E
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation; D002645:Chickens; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004527:Egg Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments; D014407:Tumor Cells, Cultured
D000941:Antigens; D004527:Egg Proteins; D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D010446:Peptide Fragments; D010047:Ovalbumin