ER egress of invariant chain isoform p35 requires direct binding to MHCII molecules and is inhibited by the NleA virulence factor of enterohaemorrhagic Escherichia coli.
Four invariant chain (Ii) isoforms assist the folding and trafficking of human MHC class II (MHCIIs). The main isoforms, Iip33 and Iip35, assemble in the ER into homo- and/or hetero-trimers. The sequential binding of up to three MHCII αβ heterodimers to Ii trimers results in the formation of pentamers, heptamers and nonamers. MHCIIs are required to overcome the p35-encoded di-arginine (RxR) ER retention motif and to allow anterograde trafficking of the complex. Here, we show that inactivation of the RxR motif requires a direct cis interaction between p35 and the MHCII, precluding ER egress of some unsaturated Ii trimers. Interestingly, as opposed to MHCII/p33 complexes, those including p35 remained in the ER when co-expressed with the NleA protein of enterohaemorrhagic Escherichia coli. Taken together, our results demonstrate that p35 influences distinctively MHCII/Ii assembly and trafficking.
Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Qué., Canada.
Maryse
M
Cloutier
Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Qué., Canada.
Catherine
C
Gauthier
Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Qué., Canada.
Jean-Simon
JS
Fortin
Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Qué., Canada.
Laetitia
L
Genève
Department of Pediatrics, UC Davis Medical Center, M.I.N.D. Institute, Sacramento, CA, USA.
Kyungho
K
Kim
Department of Microbiology and Immunology, McGill Life Sciences Complex, Bellini Pavilion, Montreal, Qué., Canada.
Samantha
S
Gruenheid
Department of Pediatrics, UC Davis Medical Center, M.I.N.D. Institute, Sacramento, CA, USA.
Jinoh
J
Kim
Laboratoire d'Immunologie Moléculaire, Département de Microbiologie et Immunologie, Université de Montréal, Montréal, Qué., Canada. Electronic address: jacques.thibodeau@umontreal.ca.
Jacques
J
Thibodeau
D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D054324:Enterohemorrhagic Escherichia coli / Q000276:immunology* / Q000472:pathogenicity; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006680:HLA Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D021382:Protein Sorting Signals / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D029968:Escherichia coli Proteins; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; C488216:NleA protein, E coli; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D037521:Virulence Factors; C045084:invariant chain
Antigen presentation; COPII; Di-arginine; Invariant chain; MHC class II; NleA