Human monoclonal autoantibody 2E7 is specific for a peptide sequence of platelet glycoprotein IIb. Localization of the epitope to IIb231-238 with an immunodominant Trp235.
2E7 is a human monoclonal IgM autoantibody that binds to a site on the heavy chain of the human platelet integrin alpha subunit glycoprotein IIb. The epitope recognized by 2E7 is stable to denaturation with sodium dodecyl sulfate and reduction of disulfide bonds but is destroyed by proteolysis with papain, chymotrypsin or elastase. By evaluating the reaction of 2E7 with a number of protein sequences from the IIb heavy chain, we have determined that the epitope is located in the octapeptide Phe-Asp-Gly-Tyr-Trp-Gly-Tyr-Ser (FDGYWGYS), corresponding to residues 231-238, and that substitution of the Trp at position 235 completely destroys the epitope. This represents the first precise localization of an epitope on the human platelet integrin IIb-IIIa or on any platelet membrane glycoprotein that is recognized by a human autoantibody.
Kunicki
T J
TJ
Blood Center of Southeastern Wisconsin, Milwaukee 53233.
Plow
E F
EF
Kekomaki
R
R
Nugent
D J
DJ
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001323:Autoantibodies; D000939:Epitopes; D006801:Humans; D016023:Integrins / Q000737:chemistry / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010447:Peptide Hydrolases; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000276:immunology*; D011489:Protein Denaturation
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D000939:Epitopes; D016023:Integrins; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; D010447:Peptide Hydrolases