Generation of CLIP from lip10

Stable Identifier
Reaction [transition]
Homo sapiens
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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

Ploegh, HL, Lagaudrière-Gesbert, C, Fiebiger, E, Bryant, PW, Lennon-Duménil, AM

Adv Immunol 2002
10748235 Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages

Chapman, HA, Ploegh, HL, Bromme, D, Driessen, C, Riese, R, Verhelst, S, Shi, GP, Li, Z, Bryant, RA

J Exp Med 2000
12748383 Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs

Camosseto, V, Lelouard, H, Pierre, P, Cappello, F, Gatti, E, David, A, Bania, J, Weber, E

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

Villadangos, JA, Farr, A, Peters, C, Wong, P, Ploegh, H, Deussing, J, Nelson, A, Nakagawa, T, Roth, W, Rudensky, AY

Science 1998
10631941 Proteases involved in MHC class II antigen presentation

Chapman, HA, Villadangos, JA, Ploegh, HL, Peters, C, Deussing, J, Driessen, C, Saftig, P, Roth, W, Shi, GP, Riese, RJ, Lennon-Duménil, AM, Bryant, RA

Immunol Rev 1999
10072072 Cathepsin S required for normal MHC class II peptide loading and germinal center development

Chapman, HA, Ploegh, HL, Villadangos, JA, Gu, L, Small, C, Riese, R, Haley, KJ, Dranoff, G, Shi, GP

Immunity 1999
Catalyst Activity

cysteine-type endopeptidase activity of Cathepsin [lysosomal lumen]

Orthologous Events
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