Linked Life Data

20820776

Source:http://linkedlifedata.com/resource/pubmed/id/20820776

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-9-27
pubmed:abstractText
During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed MIICs. This study explores an alternative HLA class II presentation pathway in leukemic blasts that involves proteasome and transporter associated with antigen processing (TAP)-dependent peptide loading. Although HLA-DR did associate with Ii, Ii silencing in the human class II-associated invariant chain peptide (CLIP)-negative KG-1 myeloid leukemic cell line did not affect total and plasma membrane expression levels of HLA-DR, as determined by western blotting and flow cytometry. Since HLA-DR expression does require peptide binding, we examined the role of endogenous antigen-processing machinery in HLA-DR presentation by CLIP(-) leukemic blasts. The suppression of proteasome and TAP function using various inhibitors resulted in decreased HLA-DR levels in both CLIP(-) KG-1 and ME-1 blasts. Simultaneous inhibition of TAP and Ii completely down-modulated the expression of HLA-DR, demonstrating that together these molecules form the key mediators of HLA class II antigen presentation in leukemic blasts. By the use of a proteasome- and TAP-dependent pathway for HLA class II antigen presentation, CLIP(-) leukemic blasts might be able to present a broad range of endogenous leukemia-associated peptides via HLA class II to activate leukemia-specific CD4(+) T cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1432-0851
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
59
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1825-38
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Alternative Ii-independent antigen-processing pathway in leukemic blasts involves TAP-dependent peptide loading of HLA class II complexes.
pubmed:affiliation
Department of Hematology, Cancer Center Amsterdam, VU Institute for Cancer and Immunology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. m.luijn@vumc.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't