SUPPRESSION OF THE ANTIBODY-RESPONSE TO A POLYMORPHIC PEPTIDE FROM THE PLATELET ALLOANTIGEN INTEGRIN BETA(3) WITH LOW-MOLECULAR-WEIGHT ANTIGEN ARRAYS

The allelic human platelet alloantigens Pl(A1)/Pl(A2) are determined b y a (33)Leu<->Pro substitution in the second disulfide loop of the int egrin beta(3) subunit of the fibrinogen receptor, alpha(IIb)beta(3) (G PIIb-IIIa). Alloantibodies to Pl(A1) cause neonatal alloimmune thrombo cytopenia, We studied the suppression of specific. Ab production to a disulfide-looped peptide spanning the polymorphic region of integrin b eta(3), (24)AWCSDEALPLGSPRCD(39) (LPL). Mice immunized with LPL couple d to OVA (LPL-OVA) produced Abs specific for LPL, When immunized anima ls were injected with low m.w. dextran heavily derivitized with LPL (D ex(low)LPL(high)), levels of Ab to LPL fell immediately and remained l ow 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, Naiv e mice given Dex(low)LPL(high) were tolerant to subsequent immunizatio n with LPL-OVA, In transfer experiments, irradiated recipients of sple en 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 ce lls, These results demonstrate that peptide arrays, by a mechanism sen sitive to molecular configuration, induce tolerance to peptide immuniz ation and suppress an ongoing, high affinity Ab response, Peptide arra ys induce the elimination or irreversible anergy of specific memory B cells and do not require a non-B spleen cell population to maintain su ppression.