MHC class II antigen processing

Stable Identifier
Reaction [transition]
Homo sapiens
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Antigen processing and loading on to MHC class II molecules occurs in late endocytic/lysosomal vesicles, where epitopes which require extensive proteolytic processing are generated (Bryant & Ploegh 2003). These late endosome/lysosomal-like compartments are enriched in MHC II and are referred to as MIICs (MHC class II compartments) (Peters et al. 1991). A variety of lysosomal proteases like cathepsins S, D, B etc. and Asparaginyl endopeptidase (AEP) are suggested to be involved in the processing of antigens to generate CD4+ T cell epitopes (Deusing et al. 1998, Shi et al. 1999, Pluger et al. 2002, Watts et al. 2005). An initial cleavage by endopeptidases (AEP) would be necessary to unlock the antigen and allow further trimming of the ends by exopeptidases (Cathepsins). In the acidic environment of the lysosome, cathepsins are generally activated by autocatalytic cleavage of a propeptide which otherwise blocks the active site.
Literature References
PubMed ID Title Journal Year
9539769 Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation

Ploegh, HL, Villadangos, JA, Peters, C, Deussing, J, Saftig, P, Roth, W

Proc Natl Acad Sci U S A 1998
10809954 Lysosomal cathepsin B plays an important role in antigen processing, while cathepsin D is involved in degradation of the invariant chain inovalbumin-immunized mice

Himeno, K, Katunuma, N, Maekawa, Y, Sakai, T, Dainichi, T, Asao, T, Zhang, T, Hanba, J, Hisaeda, H, Good, RA, Nashed, BF

Immunology 2000
16181339 Asparaginyl endopeptidase: case history of a class II MHC compartment protease

Watts, C, Mazzeo, D, Matthews, SP, Manoury, B, Moss, CX

Immunol Rev 2005
12742663 Antigen processing and presentation in human muscle: cathepsin S is critical for MHC class II expression and upregulated in inflammatory myopathies

Lautwein, A, Tolosa, E, Krause, S, Driessen, C, Morgalla, M, Mitsdörffer, M, Wiendl, H, Wienhold, W, Weber, E, Melms, A, Lochmüller, H, Overkleeft, HS, Erfurth, S

J Neuroimmunol 2003
11813165 Specific role for cathepsin S in the generation of antigenic peptides in vivo

Ploegh, HL, Driessen, C, Plüger, EB, Alfonso, C, Boes, M, Kalbacher, H, Schröter, CJ

Eur J Immunol 2002
Catalyst Activity

cysteine-type endopeptidase activity of Cathepsin [lysosomal lumen]

Orthologous Events
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