Original ArticlesAntigen capture, processing, and presentation by dendritic cells: recent cell biological studies
Section snippets
Introduction: the irony of efficient antigen handling by dendritic cells
The potency of DCs as inducers of T cell-mediated immunity can be analyzed at 3 levels: (1) antigen uptake and processing, leading to presentation of MHC-peptide complexes; (2) membrane molecules [like CD40, 54, 58, 86] and cytokines [like IL-12], leading to strong stimulation of T cell growth and differentiation; and (3) in vivo localization, leading to movement from the periphery to the T cell areas of lymphoid organs to initiate immunity. We will concentrate on the first activity,
Terminology
DCs develop from proliferating progenitors that are primarily found in bone marrow. The proliferating progenitors give rise to nonproliferating precursors, one being the blood monocyte. The precursors give rise to immature DCs that express MHC II but lack markers of other cell types such as CD3,14,16,19. The immature stage of development is specialized to internalize and process antigens, and the bulk of the MHC II molecules lie within late endosomes and lysosomes of the endocytic system,
Monitoring antigen presentation with monoclonal antibodies to MHC-peptide complexes
The above discussion has considered various functional criteria for presentation on MHC class II products. What about direct information on MHC II-peptide complexes, that is, the authentic “signal one”? Immunologists can now probe this issue better than ever before, because of the production of monoclonal antibodies to defined complexes of an MHC product and an antigenic peptide. We have used two of these: the Y-Ae antibody that recognizes a complex of I-Ab presenting an I-E peptide [35], and
Apoptotic cells as efficient substrates for dendritic cells: implications for cross priming
Can DCs process such clinically relevant substrates as transplants, tumors, and infected cells? A clue comes from transplantation, where it is known that antigens from the transplant can be presented by bone marrow-derived APCs. The terminology initially distinguished “direct” from “indirect” pathways [37]. In the former, the primed T cells see antigens directly presented on allogeneic, graft-derived DCs. In the latter, the sensitized T cells do not see antigens on the MHC products of the
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