The Invariant Chain Guides Transport of Class Ii Mhc Molecules to Endocytic Vesicles

Since antigen-presenting cells express both class I and class II MHC molecules, some mechanism must exist to prevent class II MHC molecules from binding to the same set ofanti-genic peptides as the class I molecules. When class II MHC molecule are synthesized within the RER, three pairs of class II ap chains associate with a preassembled trimer of a

VISUALIZING CONCEPTS

VISUALIZING CONCEPTS

Endogenous pathway (class I MHC)

Exogenous pathway (class II MHC)

Endogenous pathway (class I MHC)

Exogenous pathway (class II MHC)

Invariant Chain
Class I MHC

FIGURE 8-8

Separate antigen-presenting pathways are utilized for endogenous (green) and exogenous (red) antigens. The mode of antigen entry into cells and the site of antigen processing de termine whether antigenic peptides associate with class I MHC molecules in the rough endoplasmic reticulum or with class II molecules in endocytic compartments.

protein called invariant chain (Ii, CD74). This trimeric pro- from binding to the cleft while the class II molecule is within tein interacts with the peptide-binding cleft of the class II the RER (see right side of Figure 8-8). The invariant chain molecules, preventing any endogenously derived peptides also appears to be involved in the folding of the class II a and

Recycling of receptors

Clathrin coated vesicle

Early endosome pH 6.0-6.5

Early endosome pH 6.0-6.5

Golgi complex

Clathrin coated vesicle

Invariant Chain

Late endosome pH 5.0-6.0

Lysosome pH 4.5-5.0

Golgi complex

FIGURE 8-9

Late endosome pH 5.0-6.0

Lysosome pH 4.5-5.0

Generation of antigenic peptides in the endocytic processing pathway. Internalized exogenous antigen moves through several acidic compartments, in which it is degraded into peptides that ultimately associate with class II MHC molecules transported in vesicles from the Golgi complex. The cell shown here is a B cell, which internalizes antigen by receptor-mediated endocytosis, with the membrane-bound antibody functioning as an antigen-specific receptor.

p chains, their exit from the RER, and the subsequent routing of class II molecules to the endocytic processing pathway from the trans-Golgi network.

The role of the invariant chain in the routing of class II molecules has been demonstrated in transfection experiments with cells that lack the genes encoding class II MHC molecules and the invariant chain. Immunofluorescent labeling of such cells transfected only with class II MHC genes revealed class II molecules localized within the Golgi complex. However, in cells transfected with both the class II MHC genes and invariant-chain gene, the class II molecules were localized in the cytoplas-mic vesicular structures of the endocytic pathway. The invariant chain contains sorting signals in its cytoplasmic tail that directs the transport of the class II MHC complex from the trans-Golgi network to the endocytic compartments.

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  • fastolph
    What is invariant chain molecules?
    8 years ago

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