Reactome | MHC class II antigen processing

MHC class II antigen processing

Stable Identifier

R-HSA-2130706

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

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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