Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T cell activation (Science, 2007, 316:612-616)

報告日期: 2007/10/23
報告時間: 17:10/18:00
報告學生: 陳俐穎
講評老師: 楊倍昌
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Distinct pathways of antigen uptake and intracellular routing in CD4 and CD8 T Cell Activation

Sven Burgdorf, et al., Science, 316, 612-616 (2007)

 

Speaker: 陳俐穎

Commentator: 楊倍昌 老師

Date: 2007/10/23

Place: Room 602

 

Abstract

In 1976, cross-presentation of antigen presenting cells (APCs) to process exogenous antigens via MHC class I molecules was first reported. Several reports have shown that cross-presentation occurred in dendritic cells (DCs) and macrophages under some circumstances in vitro and required large amounts of antigen uptake. However, the detail intracellular routing and the mechanisms of selectively presenting antigen by APCs to CD4 or CD8 T cells in vivo remain elusive. The authors reported that mannose receptor (MR), a pattern recognition receptor (PRR), involved in cross-presentation of soluble proteins in 20061. By using OT-IOVA257-264 CD8 T cells and OT-IIOVA323-339 CD4 T cells from transgenic mice, they investigated the antigen presenting ability of MR-/- DCs and MR-/- macrophages2 to class I and class II T cells. To investigate the selective presentation of antigen by APCs, they traced the antigen uptake and intracellular routing of antigen uptake via pinocytosis, MR-, and scavenger receptor (SR, another PRR)-mediated endocytosis in MR+/+ DCs and MR+/+ macrophages. In the OVA model, DCs and macrophages cross-presented antigen to CD8 T cells only through MR- but not through SR-mediated endocytosis or pinocytosis. Moreover, the entire processing routing of presenting antigen to MHC I was extremely excluded from the MHC class II compartment. The authors concluded that the selective presentation of antigen to CD4 or CD8 T cells did not depend on large amounts of antigen uptake but the way of antigen uptake and the intracellular compartment it stayed. These findings provide a new mechanism for antigen presentation and the development of ex vivo cell-based vaccine.

 

References:

1. S. Burgdorf, V. Lukacs-Kornek, C. Kurts, J. Immunol. 176, 6770 (2006).

2. L. A. Pozzi, J. W. Maciaszek, K. L. Rock, J. Immunol. 175, 2071 (2005).