title: Naturally processed peptides spanning the HPA-1a polymorphism are efficiently generated and displayed from platelet glycoprotein by HLA-DRB3*0101-positive antigen-presenting cells.
abstract: In neonatal alloimmune thrombocytopenia, almost all human platelet antigen (HPA)-1b1b mothers who produce anti-HPA-1a antibody through carrying an HPA-1a fetus are human histocompatibility leukocyte antigen (HLA)-DRB3*0101 positive. It is predicted that the HPA-1a Leu(33) polymorphism forms part of an HLA-DRB3*0101-restricted T-helper epitope, and acts as an anchor residue for binding this class II molecule. However, it is not known whether any corresponding peptides are naturally processed and presented from platelet glycoprotein. In this study, peptides displayed by a homozygous HLA-DRB3*0101 antigen-presenting cell line were identified after pulsing with recombinant HPA-1a (Leu(33) plexin-semaphorin-integrin domain). The peptides were eluted from HLA-DR molecules, fractionated by high performance liquid chromatography, and analyzed by tandem mass spectrometry. A "nested set" of naturally presented HPA-1a-derived peptides, each containing the Trp(25)-Leu(33) core epitope, was identified, with the most abundant member being the 16-mer Met(22)-Arg(37). These peptides may provide the basis for novel treatments to tolerize the corresponding T-helper response in women at risk of neonatal alloimmune thrombocytopenia.
authors.affiliation: Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Anani Sarab
authors.forename: Michael
authors.initials: M
authors.lastname: Moss
authors.forename: Robert N
authors.initials: RN
authors.lastname: Barker
authors.forename: Stanislaw J
authors.initials: SJ
authors.lastname: Urbaniak
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism*; D000941:Antigens / Q000737:chemistry; D016824:Antigens, Human Platelet / Q000235:genetics* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000737:chemistry; D005982:Glutathione Transferase / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics*; D059826:HLA-DRB3 Chains; D006720:Homozygote; D006801:Humans; D039661:Integrin beta3; D007930:Leucine / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011110:Polymorphism, Genetic; D014364:Tryptophan / Q000737:chemistry
chemical_list: D000941:Antigens; D016824:Antigens, Human Platelet; D000939:Epitopes; D006684:HLA-DR Antigens; D059826:HLA-DRB3 Chains; C061248:ITGB3 protein, human; D039661:Integrin beta3; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D014364:Tryptophan; D005982:Glutathione Transferase; D007930:Leucine