The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/12/2163/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 11, December 7, 1998 2163-2173

Articles

Efficient Presentation of Phagocytosed Cellular Fragments on the Major Histocompatibility Complex Class II Products of Dendritic Cells

Kayo Inaba*, Shannon Turley{ddagger}, Fumiya Yamaide*, Tomonori Iyoda*, Karsten Mahnke||, Muneo Inaba§, Margit Pack||, Marion Subklewe||, Birthe Sauter||, David Sheff{ddagger}, Matthew Albert||, Nina Bhardwaj||, Ira Mellman{ddagger}, and Ralph M. Steinman||

From the * Department of Zoology, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan; the {ddagger} Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520; the § First Department of Pathology, Kansai Medical University, Osaka 570-0074, Japan; and the || Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York 10021

Cells from the bone marrow can present peptides that are derived from tumors, transplants, and self-tissues. Here we describe how dendritic cells (DCs) process phagocytosed cell fragments onto major histocompatibility complex (MHC) class II products with unusual efficacy. This was monitored with the Y-Ae monoclonal antibody that is specific for complexes of I-Ab MHC class II presenting a peptide derived from I-E{alpha}. When immature DCs from I-Ab mice were cultured for 5–20 h with activated I-E+ B blasts, either necrotic or apoptotic, the DCs produced the epitope recognized by the Y-Ae monoclonal antibody and stimulated T cells reactive with the same MHC–peptide complex. Antigen transfer was also observed with human cells, where human histocompatibility leukocyte antigen (HLA)-DR{alpha} includes the same peptide sequence as mouse I-E{alpha}. Antigen transfer was preceded by uptake of B cell fragments into MHC class II–rich compartments. Quantitation of the amount of I-E protein in the B cell fragments revealed that phagocytosed I-E was 1–10 thousand times more efficient in generating MHC–peptide complexes than preprocessed I-E peptide. When we injected different I-E– bearing cells into C57BL/6 mice to look for a similar phenomenon in vivo, we found that short-lived migrating DCs could be processed by most of the recipient DCs in the lymph node. The consequence of antigen transfer from migratory DCs to lymph node DCs is not yet known, but we suggest that in the steady state, i.e., in the absence of stimuli for DC maturation, this transfer leads to peripheral tolerance of the T cell repertoire to self.

Key Words: apoptosis • necrosis • dendritic cells • major histocompatibility complex–peptide complexes • immature dendritic cells

Address correspondence to Ralph M. Steinman, Laboratory of Cellular Physiology and Immunology, The Rockefeller University, 1230 York Ave., New York, NY 10021. Phone: 212-327-8106; Fax: 212-327-8875; E-mail: steinma{at}rockvax.rockefeller.edu

Abbreviations used: DC, dendritic cell; MIIC, MHC class II compartment.


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