The role of the Ia-invariant chain complex in the posttranslational processing and transport of Ia and invariant chain glycoproteins.

Simonis, Simonetta; Miller, Jim; Cullen, Susan E.

doi:10.4049/jimmunol.143.11.3619

Cited by 22 publications

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The invariant chain induces compact forms of class II molecules localized in late endosomal compartments

et al. 1993

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The invariant chain (Ii) binds to newly synthesized major histocompatibility complex (MHC) class II molecules and is targeted to an acidic compartment where it is degraded. To evaluate its role on the conformation and the subcellular distribution of murine MHC class II molecules we have established stable L cell transfectants expressing class II IAk heterodimers alone or in conjunction with p31 and p41 Ii chains. In these cells, class II molecules were present under three forms: alpha beta heterodimers bearing high mannose carbohydrate moieties, and fully glycosylated alpha beta heterodimers that are sensitive or resistant to sodium dodecyl sulfate dissociation at 20 degrees C. The latter class II molecules called compact heterodimers, were here highly induced in Ii-positive cells. Using in situ iodination of endosomal compartments, class II heterodimers were detected in late endosomal compartments essentially as compact forms in Ii-positive cells, and as non-compact forms in Ii-negative cells. Using confocal microscopy, IAk molecules were located in compartments distinct from early endosomes labeled with transferrin, but partially coincident with vesicles containing fluid-phase markers, and highly coincident with compartments containing large amounts of cathepsins B, D, H, and L in Ii-positive and Ii-negative cells. At the ultrastructural level, class II molecules were mostly present in multivesicular bodies, even without Ii expression. But Ii chains were needed to induce an efficient presentation of the hen egg lysozyme antigen and were sufficient to promote a major conformational change of the late endosomal, and/or lysosomal resident, class II molecules. Ii molecules are presumably playing a chaperoning function favoring the association of peptides with class II molecules in endosomal compartments.

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The invariant chain induces compact forms of class II molecules localized in late endosomal compartments

et al. 1993

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Mouse B lymphocyte specific endocytosis and recycling of MHC class II molecules.

et al. 1990

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In B lymphocytes, the processing of exogenous proteins and the subsequent binding of antigenic peptides to class II molecules encoded by the major histocompatibility complex (MHC) occurs most likely within endocytic compartments. To examine the endocytic transport of MHC class II molecules, we used (i) surface iodination followed by internalization, pronase treatment and immunoprecipitation, (ii) in situ iodination of endosomal compartments, and (iii) confocal microscopy to visualize the fate of fluorescence coupled Fab fragments. In murine I‐Ak, I‐Ek positive B lymphoma cells, cell surface MHC class II molecules are partially protected from pronase digestion after 15 min at 37 degrees C and recycled back to the cell surface within the next 30 min. The fluorescence coupled Fab fragments are delivered to juxtanuclear endocytic compartments in 15 min. In contrast to the murine B cells, L fibroblasts transfected with either I‐A alpha beta k or I‐E alpha k beta k,d fail to internalize their surface class II molecules. A fraction of class II molecules, however, is still present in endosomal compartments as detected after in situ iodination in L fibroblasts. We conclude that the recipient L fibroblasts lack one or several factors needed for the transport of MHC class II molecules from the cell surface to the endosomes. We suggest that in murine B lymphoma cells, antigenic peptides can gain access to a pool of recycling class II molecules whereas in L cells they meet newly synthesized class II molecules targeted to the endosomal compartments.

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Lead influences translational or posttranslational regulation of ia expression and increases invariant chain expression in mouse B cells

McCabe

Dias

Lawrence

1991

J. Biochem. Toxicol.

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The molecular mechanisms governing the increased cell surface expression of major histocompatibility complex (MHC) class II molecules (Ia) on lead-treated mouse B cells was investigated. Lead has been shown to directly cause a selective, two-fold increase in the B cell's surface density of both products of the I region of the mouse MHC, I-A and I-E. In the present study, Western blot analysis showed that Pb increases the total cellular pool of I-A beta-chain by twofold. The increase in cellular I-A was not found to be due to increased messenger RNA (mRNA) for either the alpha- or the beta-chain of I-A. Biosynthetic labeling studies showed that Pb increases the translation or the stability of the Ia-associated invariant chain (Ii or gamma) and possibly the beta-chain of Ia. Collectively these results suggest that Pb increases the B cell's surface Ia by influencing translational or posttranslational regulation of Ia and/or Ia-associated chains.

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The role of the Ia-invariant chain complex in the posttranslational processing and transport of Ia and invariant chain glycoproteins.

Cited by 22 publications

References 0 publications

The invariant chain induces compact forms of class II molecules localized in late endosomal compartments

The invariant chain induces compact forms of class II molecules localized in late endosomal compartments

Mouse B lymphocyte specific endocytosis and recycling of MHC class II molecules.

Lead influences translational or posttranslational regulation of ia expression and increases invariant chain expression in mouse B cells

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