Suppression of the antibody response to a polymorphic peptide from the platelet alloantigen integrin beta3 with low molecular weight antigen arrays.
The allelic human platelet alloantigens PIA1/PIA2 are determined by a 33 Leu-Pro substitution in the second disulfide loop of the integrin beta3 subunit of the fibrinogen receptor, alphaIIb beta3 (GPIIb-IIIa). Alloantibodies to PIA1 cause neonatal alloimmune thrombocytopenia. We studied the suppression of specific Ab production to a disulfide-looped peptide spanning the polymorphic region of integrin beta3, 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 8 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.
Watson
D C
DC
Department of Pediatrics and Biophysical Chemistry, John Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Reim
J
J
Dintzis
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002645:Chickens; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007231:Infant, Newborn; D039661:Integrin beta3; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007518:Isoantibodies / Q000096:biosynthesis*; D007519:Isoantigens / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010047:Ovalbumin / Q000276:immunology; D010455:Peptides / Q000235:genetics / Q000276:immunology*; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013921:Thrombocytopenia / Q000209:etiology / Q000276:immunology
D015703:Antigens, CD; D007074:Immunoglobulin G; D039661:Integrin beta3; D016023:Integrins; D007518:Isoantibodies; D007519:Isoantigens; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D010047:Ovalbumin