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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-8-11
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pubmed:abstractText |
In transplant rejection, graft versus host or autoimmune diseases T cells are mediating the pathophysiological processes. Compared to unspecific pharmacological immune suppression specific inhibition of those T cells, that are involved in the disease, would be an alternative and attractive approach. T cells are activated after their T cell receptor (TCR) recognizes an antigenic peptide displayed by the Major Histocompatibility Complex (MHC). Molecules that interact with MHC-peptide-complexes in a specific fashion should block T cells with identical specificity. Using the model of the SSX2 (103-111)/HLA-A*0201 complex we investigated a panel of MHC-peptide-specific Fab antibodies for their capacity blocking specific T cell clones. Like TCRs all Fab antibodies reacted with the MHC complex only when the SSX2 (103-111) peptide was displayed. By introducing single amino acid mutations in the HLA-A*0201 heavy chain we identified the K66 residue as the most critical binding similar to that of TCRs. However, some Fab antibodies did not inhibit the reactivity of a specific T cell clone against peptide pulsed, artificial targets, nor cells displaying the peptide after endogenous processing. Measurements of binding kinetics revealed that only those Fab antibodies were capable of blocking T cells that interacted with an affinity in the nanomolar range. Fab antibodies binding like TCRs with affinities on the lower micromolar range did not inhibit T cell reactivity. These results indicate that molecules that block T cells by competitive binding with the TCR must have the same specificity but higher affinity for the MHC-peptide-complex than the TCR.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Blocking,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A*02:01 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/HLA-A2 Antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Library,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/synovial sarcoma X breakpoint...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1879-0542
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
125
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
86-92
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19524620-Antibodies, Blocking,
pubmed-meshheading:19524620-Antibody Affinity,
pubmed-meshheading:19524620-Antigens, Neoplasm,
pubmed-meshheading:19524620-Binding, Competitive,
pubmed-meshheading:19524620-Clone Cells,
pubmed-meshheading:19524620-Epitopes,
pubmed-meshheading:19524620-Graft vs Host Disease,
pubmed-meshheading:19524620-HLA-A Antigens,
pubmed-meshheading:19524620-HLA-A2 Antigen,
pubmed-meshheading:19524620-Humans,
pubmed-meshheading:19524620-Immunoglobulin Fab Fragments,
pubmed-meshheading:19524620-Mutagenesis, Site-Directed,
pubmed-meshheading:19524620-Mutation,
pubmed-meshheading:19524620-Neoplasm Proteins,
pubmed-meshheading:19524620-Peptide Fragments,
pubmed-meshheading:19524620-Peptide Library,
pubmed-meshheading:19524620-Protein Binding,
pubmed-meshheading:19524620-Receptors, Antigen, T-Cell,
pubmed-meshheading:19524620-Repressor Proteins,
pubmed-meshheading:19524620-T-Cell Antigen Receptor Specificity,
pubmed-meshheading:19524620-T-Lymphocytes, Cytotoxic
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pubmed:year |
2009
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pubmed:articleTitle |
Fab antibodies capable of blocking T cells by competitive binding have the identical specificity but a higher affinity to the MHC-peptide-complex than the T cell receptor.
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pubmed:affiliation |
I. Med. Klinik, Saarland University Medical School, 66421 Homburg/Saar, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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