Intracellular Trafficking of MHC Class II Molecules

  • Alexander Y. Rudensky


CD4 T cells recognize peptides derived from foreign antigens in the context of self MHC class II molecules and as a consequence of positive and negative selection in the thymus are tolerant to peptides derived from self proteins. The primary function of MHC class II molecules is to survey the endocytic compartment of the host cell for antigenic peptides derived from extracellular and intracellular pathogens and communicate this information to CD4 T cells. To achieve this, an elaborate mechanism of the intracellular assembly and transport of MHC class II molecules has evolved. Foreign protein antigens enter the endocytic compartment of an antigen presenting cell (APC) via different routes of uptake including bulk fluid phase uptake, receptor mediated uptake or phagocytosis. Internalized antigens traverse through distinct endosomal subcompartments, i.e., early endosomes, late endosomes and lysosomes where they undergo proteolytic degradation producing antigenic peptides. Early biochemical studies demonstrated that MHC class II molecules intersect the endosomal compartment on their way to the cell surface thereby getting access to antigenic peptides.1 Figure 6.1 represents a simplistic view of endocytic and exocytic routes. The review of structure-functional organization of the endosomal compartment and its interactions with the secretory pathway which has emerged from recent cell biological studies goes beyond the scope of this chapter. I will therefore mainly focus on intracellular trafficking of MHC class II molecules.


Major Histocompatibility Complex Class Intracellular Trafficking Late Endosome Endocytic Pathway Endosomal Compartment 


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  • Alexander Y. Rudensky

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