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Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs

Nature volume 392, pages 86–89 (1998)Cite this article

Abstract

CD8+ cytotoxic T lymphocytes (CTLs) mediate resistance to infectious agents and tumours. Classically, CTLs recognize antigens that are localized in the cytoplasm of target cells, processed and presented as peptide complexes with class I molecules of the major histocompatibility complex (MHC)1. However, there is evidence for an exogenous pathway whereby antigens that are not expected to gain access to the cytoplasm are presented on MHC class I molecules2,3,4,5,6. The most dramatic example is the in vivo phenomenon of cross-priming7: antigens from donor cells are acquired by bone-marrow-derived host antigen-presenting cells (APCs) and presented on MHC class I molecules. Two unanswered questions concern the identity of this bone-marrow-derived cell and how such antigens are acquired. Here we show that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs. Our findings suggest a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of CTLs.

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Figure 1: Dendritic cells acquire antigen from influenza-infected cells and induce class I-restricted CTLs.
Figure 2: Antigen transfer is not due to live influenza virus or free peptide.
Figure 3: Apoptosis is required for delivery of antigen to DCs.
Figure 4: Dendritic cells and not macrophages are capable of cross-presenting apoptotic antigenic material.
Figure 5: Dendritic cells engulf apoptotic monocytes.

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Acknowledgements

We thank R. Steinman, R. Darnell, Y. Choi and T. Sakmar for advice and critical review of the manuscript; G. Kaplan and W. Hellman for assistance with the EM; and B. van Steensel for assistance with the IF.

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  1. Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, 10021, New York, USA

    Matthew L. Albert, Birthe Sauter & Nina Bhardwaj

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  3. Nina Bhardwaj
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Albert, M., Sauter, B. & Bhardwaj, N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392, 86–89 (1998). https://doi.org/10.1038/32183

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