Reactome | Generation of CLIP from lip10

Generation of CLIP from lip10

Stable Identifier

R-HSA-2130349

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen, lysosomal membrane

ReviewStatus

5/5

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The lip10 fragments bound in the nonameric complex are processed leaving only the CLIP fragment (81-105) bound to the MHC II peptide binding groove. Three cysteine proteases have been shown to be capable of digesting lip10, each with a different expression pattern among different APC. Cathepsin (Cat) S digests Ii in B cells and dendritic cells, thymic epithelial cells use Cat L and Cat L, while Cat S and F are active in macrophages (Villadangos, 2001; Bryant et al, 2002). Cat S appears to be the major enzyme involved as demonstrated by the use of specific inhibitors and of knockout experiments (Stumptner-Cuvelette et al. 2002). Following lip10 digestion, the MHC-like molecule HLA-DM induces the exchange of CLIP fragment for a highly diverse array of antigens (Denzin & Cresswell. 1995).

Literature References

PubMed ID	Title	Journal	Year
12078484	Proteolysis and antigen presentation by MHC class II molecules Bryant, PW, Lennon-Duménil, AM, Fiebiger, E, Lagaudrière-Gesbert, C, Ploegh, HL	Adv Immunol	2002
10748235	Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages Shi, GP, Bryant, RA, Riese, R, Verhelst, S, Driessen, C, Li, Z, Bromme, D, Ploegh, HL, Chapman, HA	J Exp Med	2000
12748383	Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs Bania, J, Gatti, E, Lelouard, H, David, A, Cappello, F, Weber, E, Camosseto, V, Pierre, P	Proc Natl Acad Sci U S A	2003
11853874	Multiple roles of the invariant chain in MHC class II function Stumptner-Cuvelette, P, Benaroch, P	Biochim Biophys Acta	2002
9545226	Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus Nakagawa, T, Roth, W, Wong, P, Nelson, A, Farr, A, Deussing, J, Villadangos, JA, Ploegh, H, Peters, C, Rudensky, AY	Science	1998
10631941	Proteases involved in MHC class II antigen presentation Villadangos, JA, Bryant, RA, Deussing, J, Driessen, C, Lennon-Duménil, AM, Riese, RJ, Roth, W, Saftig, P, Shi, GP, Chapman, HA, Peters, C, Ploegh, HL	Immunol Rev	1999
10072072	Cathepsin S required for normal MHC class II peptide loading and germinal center development Shi, GP, Villadangos, JA, Dranoff, G, Small, C, Gu, L, Haley, KJ, Riese, R, Ploegh, HL, Chapman, HA	Immunity	1999