Antigen Presentation and Inflammatory Responses Cross Presentation of Apoptotic Antigens

After uptake of apoptotic cells by phagocytes, the cellular components are processed and either incorporated by the phagocyte or, provided that the apoptotic protein fragments can fit into the MHC binding groove, presented to CD4+ T cells by MHC class II or to CD8+ T cells by MHC class I molecules in a process called "cross-presentation." Cross-presentation of apoptotic debris to MHC class I-restricted T cells is surprising because MHC class I-associated proteins are usually cytosolic proteins that are processed through proteosomes and subsequently enter the ER by a transporter associated with antigen processing. Further attachment to the MHC class I complex is mediated through the proteins tapasin, calnexin, and Erp57. The pathway by which the epitopes from apoptotic cells gain access to MHC class I proteins has not been fully elucidated, and it is unclear whether there is a direct phagosome to cytosol pathway, direct access to the cytosol of apoptotic antigens, or a separate phagosome that contains the MHC class I loading machinery. MHC class II presentation of apop-totic debris is more direct, as phagocytic uptake of apoptotic debris is processed through the lysosome and endoplasmic reticulum (ER), where it can attach to MHC class II molecules (Rovere-Querini and Dumitriu 2003).

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