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Voie d'immunisation et séquence d'administration de l ... - TEL

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tel-00827710, version 1 - 29 May 2013<br />

(b) Presentation of extracellular antigens on MHC-II<br />

While MHC-I molecules are expressed by all nucleated cells, only few cell types express<br />

MHC-II molecules (B cells, thymic epithelial cells, macrophages and DCs) and can thus<br />

present extracellular antigens to CD4 + T cells.<br />

Following engulfment, the exogenous antigen is partially <strong>de</strong>gra<strong>de</strong>d and the resulting pepti<strong>de</strong>s<br />

are transferred to the MHC-II compartment where they comp<strong>et</strong>e with the Class II associated<br />

invariant chain pepti<strong>de</strong> (CLIP) for binding to the pre-assembled MHC-II molecule. Then<br />

MHC molecules loa<strong>de</strong>d with pepti<strong>de</strong>s are stabilized and transported to the cell surface<br />

(Figure 3, pathway 1, orange arrows). Degradation of the engulfed antigen is <strong>de</strong>pen<strong>de</strong>nt on<br />

the acidic pH in endosomes and phagosomes, which allows the activation of lysosomal<br />

proteases required for the digestion of antigens and their loading on MHC-II molecules. Of<br />

note, endogenous pepti<strong>de</strong>s originating from endosomal proteins, proteins from plasma<br />

membrane, or from cytosolic components transferred into endosomes via autophagy can also<br />

be presented on MHC-II (Buckwalter and Albert, 2009) (Figure 3, pathway 2, green<br />

arrows).<br />

Figure 3. Generation of MHC-II-pepti<strong>de</strong> complexes from endogenous and exogenous antigen.<br />

The pathway 1 (orange arrows) represents the presentation of exogenous antigen on MHC-II. The<br />

pathway 2 (green arrows) corresponds to the presentation of endogenous antigen on MHC-II<br />

molecules. Figure from Buckwalter <strong>et</strong> al., 2009.<br />

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