title: Seminal plasma peptides may determine maternal immune response that alters success or failure of pregnancy in the abortion-prone CBAxDBA/2 model.
abstract: Spontaneous abortion (resorption) in the DBA/2-mated CBA/J mouse involves a deficiency in Treg cell activity against paternal antigens at the time of mating. Preimmunization of female CBA/J by BALB/c splenocytes, but not DBA/2 splenocytes, protects against subsequent abortions after a CBAxDBA/2 mating. Previous immunogenetic studies with BALB/cxDBA/2 recombinants have indicated that H-2(d)-restricted presentation of a single minor non-H-2(d) peptide might be responsible for protection, while the product of a second independent allele might promote abortions. Using brefeldin-treated BALB/c and DBA/2 splenocytes, we found that incubation in BALB/c seminal plasma rendered DBA/2 splenocytes protective and DBA/2 seminal plasma eliminated protection. The active protective moiety was <10 kD consistent with a peptide. DBA/2 seminal plasma contained a <10-kD peptide that boosted the abortion rate. Maternal H-2(k) CBA/J splenocytes were unable to present the protective activity. Amicon fractionation also unmasked a <10-kD activity in DBA/2 seminal plasma that could boost abortion rates when presented by BALB/c splenocytes. SELDI-TOF mass spectrometry proteomic analysis of <10-kD filtrates reproducibly detected 1416, 1468, 1774 D peptides in BALB/c that were reduced or absent in DBA/2, and the presence of 2662, 4559 and 5320 D molecules in DBA/2, the latter two definitely not present in BALB/c. Direct antigen presentation of paternal H-2(d)-restricted paternal peptides (600-1800 D) may prevent the rejection of the CBAxDBA/2 embryos, and larger sized peptides may bind to immunizing splenocytes and augment abortion mechanisms.
authors.affiliation: Department of Medicine, Molecular Medicine & Pathology, Ob-Gyn., McMaster University, Health Sciences Centre, Room 3H1E, Hamilton, Ontario, Canada L8S 4K1; Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: clarkd@mcmaster.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Clark
authors.forename: Mona
authors.initials: M
authors.lastname: Rahmati
authors.forename: Claudia
authors.initials: C
authors.lastname: Gohner
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Udo R
authors.initials: UR
authors.lastname: Markert
authors.forename: Gerard
authors.initials: G
authors.lastname: Chaouat
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology* / Q000628:therapy; D000818:Animals; D017951:Antigen Presentation; D002478:Cells, Cultured; D004198:Disease Susceptibility; D005260:Female; D064532:Histocompatibility Antigen H-2D / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy / Q000276:immunology; D012661:Semen / Q000276:immunology / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D064532:Histocompatibility Antigen H-2D; D015778:Minor Histocompatibility Antigens; D010446:Peptide Fragments
keywords: IDO; IVF; Immunotherapy; Pregnancy; Proteomics; SELDI-TOF; SP; Seminal plasma; Spontaneous abortion; in vitro fertilization and embryo transfer; indoleamine 2,3-dioxygenase; seminal plasma; surface-enhanced laser densitometry and isolation – time of flight