title: Predicted indirectly recognizable HLA epitopes presented by HLA-DR correlate with the de novo development of donor-specific HLA IgG antibodies after kidney transplantation.
abstract: BACKGROUND
  HLA class-I mismatches selectively induce antibody formation after kidney transplantation. The de novo development of donor-specific IgG HLA class-I antibodies may be dependent on the HLA class-II background of the patient by presenting T-helper epitopes within the recognized HLA class-I antigens.
  
  
  METHODS
  The correlation between antibody production against mismatched donor human leukocyte antigens (HLA) class I and the number of HLA class II-restricted predicted indirectly recognizable HLA epitopes (PIRCHE-II) in the respective HLA class-I mismatches was investigated. To this end, we analyzed sera taken after nephrectomy from a cohort of 21 non-immunized individuals that received a renal transplant.
  
  
  RESULTS
  Fourty-nine HLA class-I mismatches were found which all contained immunogenic eplets according to HLAMatchmaker. Donor specific HLA antibody responses were detected against 38 HLA class-I mismatches after nephrectomy. These mismatches were found to contain a larger number of PIRCHE-II when compared to mismatches which did not induce donor specific HLA antibodies. Most PIRCHE-II (68%) were not part of an eplet as defined by HLAMatchmaker.
  
  
  CONCLUSIONS
  Our data suggest that presentation of donor-derived HLA class-I peptides by recipient HLA class-II molecules plays a significant role in de novo development of donor-specific IgG HLA antibodies.
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Henny G
authors.initials: HG
authors.lastname: Otten
authors.forename: Jorg J A
authors.initials: JJ
authors.lastname: Calis
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
authors.forename: Arjan D
authors.initials: AD
authors.lastname: van Zuilen
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
mesh_terms: D000906:Antibodies / Q000097:blood / Q000276:immunology*; D003198:Computer Simulation; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D000939:Epitopes; D006680:HLA Antigens; D006684:HLA-DR Antigens; D007074:Immunoglobulin G