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Characterization of autoantigenic epitopes on platelet glycoprotein
IIb/IIIa using random peptide libraries
RD Bowditch, P Tani, KC Fong and R McMillan
The Scripps Research Institute, La Jolla, CA 92037, USA.
Most patients with chronic immune thrombocytopenic purpura (ITP) have
autoantibodies directed against the glycoprotein (GP) IIb/IIIa complex. We
have used a filamentous phage library that displays random linear
hexapeptides to identify peptide sequences recognized by these
autoantibodies. Plasma antibody eluates from two patients were used to
select for phage displaying autoantibody-reactive peptides. From patient
ITP-1 (known to have two distinct autoantibodies), we identified
anti-GPIIb/IIIa antibody-specific phage encoding the peptide sequences
Arg-Glu-Lys-Ala-Lys-Trp (REKAKW) and Pro-Val-Val-Trp-Lys-Asn (PVVWKN).
Patient ITP-2 bound phage encoding the hexapeptide sequence
Arg-Glu-Leu-Leu-Lys-Met. Each phage showed saturable dose-dependent binding
to immobilized autoantibody, and binding could be blocked with purified
GPIIb/IIIa. Patient ITP-1 autoantibody recognition of phage encoding REKAKW
could be blocked with a synthetic peptide derived from the GPIIIa
cytoplasmic tail; however, the PVVWKN was not. Using sequential overlapping
peptides from the GPIIIa cytoplasmic region, an epitope for ITP-1 was
localized to the sequence Arg-Ala-Arg-Ala-Lys-Trp (GPIIIa 734-739).
Inhibition studies using synthetic peptides showed that phage REKAKW and
PVVWKN were recognized by distinct autoantibodies from patient ITP-1. To
determine whether individual patients with ITP possessed autoantibodies
that recognize similar antigenic determinants on GPIIb/IIIa, the three
phage were tested for binding to five other ITP patient autoantibodies. The
phage encoding the peptide PVVWKN was found to bind ITP-1 and one other
patient autoantibody. This result suggests that ITP patients recognize a
limited number of shared epitopes.
Volume 88,
Issue 12,
pp. 4579-4584,
12/15/1996
Copyright © 1996 by The American Society of Hematology
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