PMID- 10631941
OWN - NLM
STAT- MEDLINE
DCOM- 20000214
LR  - 20190915
IS  - 0105-2896 (Print)
IS  - 0105-2896 (Linking)
VI  - 172
DP  - 1999 Dec
TI  - Proteases involved in MHC class II antigen presentation.
PG  - 109-20
AB  - Major histocompatibility complex class II antigen presentation requires the
      participation of lysosomal proteases in two convergent processes. First, the
      antigens endocytosed by the antigen-presenting cells must be broken down into
      antigenic peptides. Second, class II molecules are synthesized with their
      peptide-binding site blocked by invariant chain (Ii), and they acquire the
      capacity to bind antigens only after Ii has been degraded in the compartments
      where peptides reside. The study of genetically modified mice deficient in single
      lysosomal proteases has allowed us to determine their role in these processes.
      Cathepsins (Cat) B and D, previously considered major players in MHC class II
      antigen presentation, are dispensable for degradation of Ii and for generation of
      several antigenic determinants. By contrast, Cat S plays an essential role in
      removal of Ii in B cells and dendritic cells, whereas Cat L apparently does so in
      thymic epithelial cells. Accordingly, the absence of Cat S and L have major
      consequences for the onset of humoral immune responses and for T-cell selection, 
      respectively. It is likely that other as yet uncharacterized lysosomal enzymes
      also play a role in Ii degradation and in generation of antigenic determinants.
      Experiments involving drugs that interfere with protein traffic suggest that more
      than one mechanism for Ii removal, probably involving different proteases, can
      co-exist in the same antigen-presenting cell. These findings may allow the
      development of protease inhibitors with possible therapeutic applications.
FAU - Villadangos, J A
AU  - Villadangos JA
AD  - Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
FAU - Bryant, R A
AU  - Bryant RA
FAU - Deussing, J
AU  - Deussing J
FAU - Driessen, C
AU  - Driessen C
FAU - Lennon-Dumenil, A M
AU  - Lennon-Dumenil AM
FAU - Riese, R J
AU  - Riese RJ
FAU - Roth, W
AU  - Roth W
FAU - Saftig, P
AU  - Saftig P
FAU - Shi, G P
AU  - Shi GP
FAU - Chapman, H A
AU  - Chapman HA
FAU - Peters, C
AU  - Peters C
FAU - Ploegh, H L
AU  - Ploegh HL
LA  - eng
GR  - AI34893/AI/NIAID NIH HHS/United States
GR  - CA14051/CA/NCI NIH HHS/United States
GR  - HL48261/HL/NHLBI NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Immunol Rev
JT  - Immunological reviews
JID - 7702118
RN  - 0 (Histocompatibility Antigens Class II)
RN  - EC 3.4.- (Cathepsins)
RN  - EC 3.4.- (Endopeptidases)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.22.1 (Cathepsin B)
RN  - EC 3.4.22.15 (CTSL protein, human)
RN  - EC 3.4.22.15 (Cathepsin L)
RN  - EC 3.4.22.15 (Ctsl protein, mouse)
RN  - EC 3.4.22.27 (cathepsin S)
RN  - EC 3.4.23.5 (Cathepsin D)
SB  - IM
MH  - Animals
MH  - *Antigen Presentation
MH  - Cathepsin B/metabolism
MH  - Cathepsin D/metabolism
MH  - Cathepsin L
MH  - Cathepsins/metabolism
MH  - Cell Differentiation
MH  - Cysteine Endopeptidases
MH  - Dendritic Cells/cytology/enzymology/immunology
MH  - Endopeptidases/*metabolism
MH  - Histocompatibility Antigens Class II/*metabolism
MH  - Humans
MH  - Mice
MH  - Models, Biological
RF  - 72
EDAT- 2000/01/13 09:00
MHDA- 2000/02/19 09:00
CRDT- 2000/01/13 09:00
PHST- 2000/01/13 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 2000/01/13 09:00 [entrez]
AID - 10.1111/j.1600-065x.1999.tb01360.x [doi]
PST - ppublish
SO  - Immunol Rev. 1999 Dec;172:109-20. doi: 10.1111/j.1600-065x.1999.tb01360.x.