The MHC class II β chain cytoplasmic tail overcomes the invariant chain p35-encoded endoplasmic reticulum retention signal

被引:33
作者
Khalil, H
Brunet, A
Saba, I
Terra, R
Sékaly, RP
Thibodeau, J
机构
[1] Univ Montreal, Fac Med, Dept Microbiol & Immunol, Lab Immunol Mol, Montreal, PQ H3C 3J7, Canada
[2] Univ Montreal, Fac Med, Dept Microbiol & Immunol, Immunol Lab, Montreal, PQ H3C 3J7, Canada
[3] McGill Univ, Sch Med, Dept Expt Med, Montreal, PQ H3G 1A4, Canada
[4] Univ Montreal, Ctr Hosp, Ctr Rech, Hop Hotel Dieu,Lab Immunol, Montreal, PQ H2W 1T8, Canada
关键词
antigen presentation; di-arginine; HLA; lip35; R-X-R;
D O I
10.1093/intimm/dxg124
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The human-specific p35 isoform of the invariant chain (Ii) includes an R-X-R endoplasmic reticulum (ER) retention motif that is inactivated upon HLA-DR binding. Although the masking is assumed to involve the cytoplasmic tails of class II molecules, the mechanism underlying this function remains to be investigated. Moreover, in light of the polymorphic nature of the class II cytosolic tails, little is known about the capacity of various isotypes or alleles to overcome the retention signal of Iip35. To gain further insights into these issues, we first addressed the proposed role of the HLA-DR cytoplasmic tails. As shown by flow cytometry, the presence of lip35 in transfected HeLa cells prevented surface expression of HLA-DR molecules lacking their cytoplasmic tails (DRalphaTM/betaTM). These truncated class II molecules and Iip35 accumulated in the ER, and co-localized with calnexin, as determined by confocal microscopy. Sensitivity of DRalphaTM/betaTM to endoglycosidase H treatment confirmed that these molecules do not reach the trans-Golgi network when associated with lip35. Further characterization revealed that the beta chain cytosolic tail is critical for efficient ER egress of class II/Iip35 complexes. Interestingly, our results clearly demonstrate for the first time that DP and Do isotypes can also overcome the retention motif of Iip35 through a mechanism involving their very distinctive polymorphic beta chain cytoplasmic tails. Altogether, these results further dissect the masking of di-basic retention signals, and emphasize the interplay between class II molecules and Ii for the transport of the complex to the endocytic pathway.
引用
收藏
页码:1249 / 1263
页数:15
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