Phagosomes are competent organelles for antigen cross-presentation

Speaker: 錢鵬如                              Date: 11/19/2003; 13:00-14:00

Commentator: 葉才明 老師                       Place: Room 601

Abstract:

    Cross-presentation is the process whereby professional APCs, mainly dendritic cells and macrophages, prime CD8⁺ T cells by presenting exogenous antigens on MHC class I molecules and this process is important in defense of intracellular pathogens and the induction of tumor immunity (1). However the molecular mechanisms of cross-presentation are still unclear. Previous study showed that phagosomes were formed by direct association and fusion of ER to the plasma membrane during early phagocytosis (2). In this paper, authors showed that Sec61 was recruited into the phagosomes and mediated the retrotranslocation of exogenous proteins from the phagosome into the cytosol of the J774 murine macrophage. They also found that proteasomes were associated with the cytosolic side of the phagosome membrane and by using MG-132, the proteasome inhibitor, the polyubiquitinated proteins were accumulated on the phagosomes. In addition to proteasome, they also found that the TAP1 and the peptide/MHC I complex were presented on phagosomes and the ability of macrophages to elicit a CD8⁺ T cell response was lost in TAP deficient mice. Furthermore, cross-presentation still could be observed in the macrophages treated with brefeldin A suggesting that the phagosome origin of the peptide/MHC class I complexes is involved in CD8⁺ T cell activation. According to these findings, the authors demonstrated that after the exogenous proteins were exported from phagosomes through Sec61, they were degraded by proteasome into peptides, shuttled back into the phagosomes by TAP and loaded on the MHC class I molecules on the inside of the phagosome membrane (3). The molecular mechanism of cross-presentation has been proposed but the importance in vivo remains further investigation.

References:

1.      Melief, C.J.M. Regulation of cytotoxic T lymphocyte response by dendritic cells: peaceful coexistence of cross-priming and direct priming? Eur. J. Immunol. 33: 2645-2654, 2003.

2.      G.agnon, E. et al. Endoplasmic reticulum-mediated phagocytosis is a mechanism of entry into macrophages. Cell 110: 119-131, 2002.

3.  Houde, M. et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 425: 402-406, 2003.