Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-6-26
pubmed:abstractText
MHC class II molecules display antigenic peptides on cell surfaces for recognition by CD4(+) T cells. Proteolysis is required in this process both for degradation of invariant chain (Ii) from class II-Ii complexes to allow subsequent binding of peptides, and for generation of the antigenic peptides. The cysteine endoprotease, cathepsin S, mediates Ii degradation in human and mouse antigen-presenting cells. Studies described here examine the functional significance of cathepsin S inhibition on antigen presentation and immunity. Specific inhibition of cathepsin S in A20 cells markedly impaired presentation of an ovalbumin epitope by interfering with class II-peptide binding, not by obstructing generation of the antigen. Administration of a cathepsin S inhibitor to mice in vivo selectively inhibited activity of cathepsin S in splenocytes, resulting in accumulation of a class II-associated Ii breakdown product, attenuation of class II-peptide complex formation, and inhibition of antigen presentation. Mice treated with inhibitor had an attenuated antibody response when immunized with ovalbumin but not the T cell-independent antigen TNP-Ficoll. In a mouse model of pulmonary hypersensitivity, treatment with the inhibitor also abrogated a rise in IgE titers and profoundly blocked eosinophilic infiltration in the lung. Thus, inhibition of cathepsin S in vivo alters Ii processing, antigen presentation, and immunity. These data identify selective inhibition of cysteine proteases as a potential therapeutic strategy for asthma and autoimmune disease processes.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-11134173, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1311249, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1328388, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1380674, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1448172, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1496399, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1588042, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1656276, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1694878, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1826010, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1913281, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-1956401, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2033257, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2119890, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2185332, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2190094, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2474542, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2517209, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2537618, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2778316, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2831066, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2923380, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-2925452, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-3126253, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-3287381, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-3487084, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7477400, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7519244, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7595228, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7596415, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7606781, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7648393, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7650671, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7679955, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7699337, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7722450, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7751647, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7922377, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-7995953, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8086833, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8157683, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8177316, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8177317, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8177319, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8293464, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8405375, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8409392, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8483910, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8612130, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8666891, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8689559, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8724005, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8810244, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8871612, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8976171, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-8981913, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-9105036, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-9160833, http://linkedlifedata.com/resource/pubmed/commentcorrection/9616206-9254653
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9738
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2351-63
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
More...