Suppression of the antibody response to a polymorphic peptide from the platelet alloantigen integrin β3 with low molecular weight antigen arrays

Douglas C. Watson, Johannes Reim, Howard M. Dintzis

Research output: Contribution to journalArticlepeer-review

Abstract

The allelic human platelet alloantigens Pl(A1)/Pl(A2) are determined by a 33Leu mutually implies Pro substitution in the second disulfide loop of the integrin β3 subunit of the fibrinogen receptor, α(IIb)β3 (GPIIb-IIIa). Alloantibodies to Pl(A1) cause neonatal alloimmune thrombocytopenia. We studied the suppression of specific Ab production to a disulfide-looped peptide spanning the polymorphic region of integrin β3, 24AWCSDEALPLGSPRCD39 (LPL). Mice immunized with LPL coupled to OVA (LPL- OVA) produced Abs specific for LPL. When immunized animals were injected with low m.w. dextran heavily derivitized with LPL (Dex(low)LPL(high)), levels of Ab to LPL fell immediately and remained low 1 mo later. Both high affinity and total Abs were affected. Arrays with lower peptide density or a high m.w. backbone did not induce well sustained suppression. Abs to OVA were unaffected by the arrays. Naive mice given Dex(low)LPL(high) were tolerant to subsequent immunization with LPL-OVA. In transfer experiments, irradiated recipients of spleen cells or purified B cells from animals suppressed with Dex(low)LPL(high) did not respond to LPL-OVA. Spleen cells from suppressed animals did not suppress the response to LPL-OVA in recipients of immune B cells. These results demonstrate that peptide arrays, by a mechanism sensitive to molecular configuration, induce tolerance to peptide immunization and suppress an ongoing, high affinity Ab response. Peptide arrays induce the elimination or irreversible anergy of specific memory B cells and do not require a non-B spleen cell population to maintain suppression.

Original languageEnglish (US)
Pages (from-to)2443-2450
Number of pages8
JournalJournal of Immunology
Volume156
Issue number7
StatePublished - Apr 1 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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