Linked Life Data

12902494

Source:http://linkedlifedata.com/resource/pubmed/id/12902494

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-8-6
pubmed:abstractText
mAb HC-10 loses its reactivity with HLA class I (HLA-I) H chain (HC) following its association with beta(2)-microglobulin (beta(2)m). Furthermore, the HC-10 defined epitope appears to be involved in the pathogenesis of spondyloarthropathies, because HC-10 reduced their incidence in HLA-B27(+)beta(2)m degrees /MHC class II knockout mice. This study has characterized the determinant recognized by HC-10. Panning of a phage display peptide library with HC-10 resulted in isolation of the motif PxxWDR, which could be aligned with P57, W60, D61, and R62 of the first domain of the HLA-I HC allospecificities reactive with HC-10. The (55)EGPEYWDR(N/E)T(64) (p-1) is the shortest motif-bearing peptide that reacts with HC-10 and inhibits its binding to soluble HLA-B7 HC, irrespective of whether N (p-1a) or E (p-1b) is present at position 63. By contrast, HC-10 did not react with six additional peptides, each bearing motif amino acid substitutions present in HC-10-not-reactive HLA-I allospecificities. The p-1-derived Qp-1, synthesized with the additional conserved Q54, which displays the highest in vitro reactivity with HC-10, was the only one to induce in mice IgG resembling HC-10 in their fine specificity. Mapping of the HC-10-defined determinant suggests that the lack of mAb reactivity with beta(2)m-associated HLA-I HC is caused by blocking by the peptide in the groove of beta(2)m-associated HLA-I HC, though a role of HC conformational changes following its association with beta(2)m cannot be excluded. This information contributes to our understanding of the molecular basis of the antigenic profiles of beta(2)m-free and beta(2)m-associated HLA-I HC and may serve to develop active specific immunotherapy of spondyloarthropathies.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
171
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1918-26
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12902494-Amino Acid Motifs, pubmed-meshheading:12902494-Animals, pubmed-meshheading:12902494-Antibodies, Monoclonal, pubmed-meshheading:12902494-Antibody Specificity, pubmed-meshheading:12902494-Bacteriophage M13, pubmed-meshheading:12902494-Binding, Competitive, pubmed-meshheading:12902494-Binding Sites, Antibody, pubmed-meshheading:12902494-Cell Line, pubmed-meshheading:12902494-Computer Simulation, pubmed-meshheading:12902494-Epitope Mapping, pubmed-meshheading:12902494-Female, pubmed-meshheading:12902494-HLA Antigens, pubmed-meshheading:12902494-Histocompatibility Antigens Class I, pubmed-meshheading:12902494-Humans, pubmed-meshheading:12902494-Injections, Intraperitoneal, pubmed-meshheading:12902494-Mice, pubmed-meshheading:12902494-Mice, Inbred BALB C, pubmed-meshheading:12902494-Models, Molecular, pubmed-meshheading:12902494-Molecular Mimicry, pubmed-meshheading:12902494-Peptide Fragments, pubmed-meshheading:12902494-Protein Binding, pubmed-meshheading:12902494-Protein Subunits, pubmed-meshheading:12902494-Tumor Cells, Cultured, pubmed-meshheading:12902494-beta 2-Microglobulin
pubmed:year
2003
pubmed:articleTitle
Beta 2-microglobulin-free HLA class I heavy chain epitope mimicry by monoclonal antibody HC-10-specific peptide.
pubmed:affiliation
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, Bari, Italy.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't