Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain (Science, 2008, 322:1705-1710)

報告日期: 2009/03/24
報告時間: 15:10/16:00
報告學生: 顏嘉良
講評老師: 林以行
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980324-1.pdf

http://basicmed.med.ncku.edu.tw/admin/up_img/980324-1Supp.pdf

Regulation of dendritic cell migration by CD74, the MHC class II-associated invariant chain

Gabrielle Faure-André, et al. Science 322, 1705-1710 (2008)

 

Speaker: 顏嘉良

Commentator: 林以行老師

Time: 2009-3-24 15:10-16:00

Place: Room 602

 

Abstract:

  Dendritic cells (DCs) are professional antigen-presenting cells which initiate primary immune responses by presenting pathogen-associated antigens to T cells by MHC-class II molecules.  MHC class II-associated invariant chain (Ii, CD74) is associated with MHC-class II molecules to prevent peptide binding in the endoplasmic reticulum.  Ii also acts as a chaperone protein to target the MHC-class II molecules to a low-pH endosomal compartment where peptide loading occur.  Moreover, Ii was shown to associate with myosin II and CD44, which known to regulate cell locaomotion.  These findings suggest that there are common regulatory mechanisms involved in both antigen presentation and cell migration.  In this paper, the authers found that Ii functions as a coordinator for antigen processing and cell motility in DCs.  First, they found that Ii-deficient DCs in mice migrated more efficiently from skin to lymph node compared with wild-type DCs.  By measuring the velocity of cell migration in fabricated microchannels, the authors found that wild-type DCs oscillate between high and low motility phases.  However, the low motility phases occurred less frequiently in Ii-deficient DCs, resulting in an overal high velocutiy.   They also found that the migratory capacity was decreased in cathepsin S (CatS)-deficient DCs, which Ii accumulate in the endolysosome.  In the absence of CatS, the localiztion of motor protein myosin II with Ii was increased and the amout of activated myosin II decreased.  Finally, the authors found that transiently increased Ii synthesis induced by lipopolysaccharide (LPS) enhace the association of Ii with myosin II and negativly regulate DC migration.  These findings suggest that Ii regulates DC migration by retaining myosin II in the endolysosome.  Ii regulates both antigen processing and cell migration in DCs may facillitate antigen detection and presentation in the process of DC maturation.

 

References:

1.         Veronika Lukacs-Kornek and Shannon J. Turley.  Chaperone Puts the Brakes On. Science, 322, 1640-1641 (2009)

2.         T. Lammermann et al., Rapid leukocyte migration by integrinindependent flowing and squeezing. Nature, 453, 51-57 (2008).