The invariant chain transports TNF family member CD70 to MHC class II compartments in dendritic cells.
CD70 is a TNF-related transmembrane molecule expressed by mature dendritic cells (DCs), which present antigens to T cells via major histocompatibility complex (MHC) molecules. In DCs, CD70 localizes with MHC class II molecules in late endosomal vesicles, known as MHC class II compartments (MIICs). MIICs are transported to the immune synapse when a DC contacts an antigen-specific CD4(+) T cell. Consequently, MHC class II and CD70 are simultaneously exposed to the T cell. Thereby, T-cell activation via the antigen receptor and CD70-mediated co-stimulation are synchronized, apparently to optimize the proliferative response. We report here that the invariant chain (Ii), a chaperone known to transport MHC class II to MIICs, performs a similar function for CD70. CD70 was found to travel by default to the plasma membrane, whereas Ii coexpression directed it to late endosomes and/or lysosomes. In cells containing the MHC class II presentation pathway, CD70 localized to MIICs. This localization relied on Ii, since transport of CD70 from the Golgi to MIICs was impeded in Ii-deficient DCs. Biophysical and biochemical studies revealed that CD70 and Ii participate in an MHC-class-II-independent complex. Thus, Ii supports transport of both MHC class II and CD70 to MIICs and thereby coordinates their delivery to CD4(+) T cells.
Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Wilbert
W
Zwart
Victor
V
Peperzak
Evert
E
de Vries
Anna M
AM
Keller
Gerda
G
van der Horst
Elise A M
EA
Veraar
Ulf
U
Geumann
Hans
H
Janssen
Lennert
L
Janssen
Shalin H
SH
Naik
Jacques
J
Neefjes
Jannie
J
Borst
D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053282:CD27 Ligand / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D011992:Endosomes / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008546:Melanoma, Experimental; D051379:Mice; D018345:Mice, Knockout; D021381:Protein Transport / Q000235:genetics
D000944:Antigens, Differentiation, B-Lymphocyte; D053282:CD27 Ligand; D000949:Histocompatibility Antigens Class II; C045084:invariant chain