title: HLAMatchmaker algorithm is not a suitable tool to predict the alloreactive cytotoxic T-lymphocyte response in vitro.
abstract: Both donor-specific anti-human leukocyte antigen (HLA) antibodies and cytotoxic T lymphocytes are important mediators of graft rejection. HLAMatchmaker determines the amino acid triplets on antibody-accessible sites of the HLA molecule that are not shared between patient and donor. A previous study showed a strong positive correlation between the number of triplet mismatches and the percentage of individuals producing HLA antibodies. In the present study, we tested whether the number of triplet mismatches is predictive for the cytotoxic T-lymphocyte precursor (CTLp) frequency in vitro. The analysis was performed on 108 HLA-DRB1 and DQB1 identical patient-donor combinations registered by the Europdonor foundation, with a single HLA class I mismatch and in healthy responder-stimulator combinations mismatched for at least one HLA class I antigen. The results show that there is no strong correlation between the number of triplet mismatches and the CTLp frequency. Even in the case of zero triplet mismatches, a high CTLp frequency can be found. This lack of correlation is probably caused by the fact that HLAMatchmaker considers only triplets on antibody-accessible positions, whereas CTLs also recognize other epitopes on the HLA molecule, including the bound peptides.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands. dankers@ikr.nl
authors.forename: Marlies K A
authors.initials: MK
authors.lastname: Dankers
authors.forename: Martin B A
authors.initials: MB
authors.lastname: Heemskerk
authors.forename: Rene J
authors.initials: RJ
authors.lastname: Duquesnoy
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000465:Algorithms; D006683:HLA-DQ Antigens / Q000276:immunology; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000276:immunology; D011237:Predictive Value of Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007518:Isoantibodies