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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1998-12-21
|
| pubmed:abstractText |
The human blood coagulation factor VIII C2 domain (Ser2173-Tyr2332) contains an epitope recognized by most polyclonal inhibitory anti-factor VIII alloantibodies and autoantibodies. We took advantage of the differential reactivity of inhibitory antibodies with human and porcine factor VIII and mapped a major determinant of the C2 epitope by using a series of active recombinant hybrid human/porcine factor VIII molecules. A series of five C2-specific human antibodies and a murine anti-factor VIII monoclonal antibody, NMC-VIII/5, inhibited a hybrid containing a substitution of porcine sequence for Glu2181-Val2243 significantly less than human factor VIII. In contrast, four of the five patient antibodies and NMC-VIII/5 inhibited a hybrid containing a substitution of porcine sequence for Thr2253-Tyr2332 equally well as human factor VIII. Thus, a major factor VIII inhibitor epitope determinant is bounded by Glu2181-Val2243 at the NH2-terminal end of the C2 domain. Because C2 inhibitors block the binding of factor VIII to phospholipid and von Willebrand factor, for which binding sites have been localized to Thr2303-Tyr2332, these results imply that the segment bounded by Glu2181-Val2243 also is involved in these macromolecular interactions.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Factor VIII,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/von Willebrand Factor
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
92
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
3701-9
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9808564-Amino Acid Sequence,
pubmed-meshheading:9808564-Amino Acid Substitution,
pubmed-meshheading:9808564-Animals,
pubmed-meshheading:9808564-Antibodies, Monoclonal,
pubmed-meshheading:9808564-Cross Reactions,
pubmed-meshheading:9808564-Epitopes,
pubmed-meshheading:9808564-Factor VIII,
pubmed-meshheading:9808564-Hemophilia A,
pubmed-meshheading:9808564-Humans,
pubmed-meshheading:9808564-Macromolecular Substances,
pubmed-meshheading:9808564-Molecular Sequence Data,
pubmed-meshheading:9808564-Phospholipids,
pubmed-meshheading:9808564-Protein Structure, Tertiary,
pubmed-meshheading:9808564-Recombinant Fusion Proteins,
pubmed-meshheading:9808564-Sequence Alignment,
pubmed-meshheading:9808564-Sequence Homology, Amino Acid,
pubmed-meshheading:9808564-Species Specificity,
pubmed-meshheading:9808564-Structure-Activity Relationship,
pubmed-meshheading:9808564-Swine,
pubmed-meshheading:9808564-von Willebrand Factor
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Residues Glu2181-Val2243 contain a major determinant of the inhibitory epitope in the C2 domain of human factor VIII.
|
| pubmed:affiliation |
Emory University, Atlanta, GA; Holland Laboratory, American Red Cross, Rockville, MD, USA.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|