title: HLA-DPB1 mismatching results in the generation of a full repertoire of HLA-DPB1-specific CD4+ T cell responses showing immunogenicity of all HLA-DPB1 alleles.
abstract: Clinical studies have indicated that HLA-DPB1 functions as a classical transplantation antigen in allogeneic stem cell transplantation. Mismatching for HLA-DPB1 was associated with an increased risk of graft-versus-host disease (GVHD), but also a decreased risk of disease relapse. However, specific HLA-DPB1 mismatches were associated with poor clinical outcome. It was suggested that this unfavorable effect was caused by a difference in immunogenicity between HLA-DPB1 alleles. To analyze whether immunogenicity of HLA-DPB1 mismatches could be predicted based on the presence or absence of specific amino acid sequences we developed a model to generate allo-HLA-DPB1 responses in vitro. We tested in total 48 different stimulator/responder combinations by stimulating CD4(+) T cells from 5 HLA-DPB1 homozygous individuals with the same antigen-presenting cells transduced with different allo-HLA-DPB1 molecules. HLA-DPB1 molecules used for stimulation comprised 76% to 99% of HLA-DPB1 molecules present in different ethnic populations. We show that all HLA-DPB1 mismatches as defined by allele typing resulted in high-frequency immune responses. Furthermore, we show that crossrecognition of different HLA-DPB1 molecules is a broadly observed phenomenon. We confirm previously described patterns in crossrecognition, and demonstrate that a high degree in similarity between HLA-DPB1 molecules is predictive for crossrecognition, but not for immunogenicity.
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. c.e.rutten@lumc.nl
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Rutten
authors.forename: Simone A P
authors.initials: SA
authors.lastname: van Luxemburg-Heijs
authors.forename: Edith D
authors.initials: ED
authors.lastname: van der Meijden
authors.forename: Marieke
authors.initials: M
authors.lastname: Griffioen
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Roel
authors.initials: R
authors.lastname: Willemze
authors.forename: J H Frederik
authors.initials: JH
authors.lastname: Falkenburg
mesh_terms: D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics* / Q000276:immunology*; D006682:HLA-DP Antigens / Q000235:genetics* / Q000276:immunology*; D059868:HLA-DP beta-Chains; D006367:HeLa Cells; D006801:Humans; D033581:Stem Cell Transplantation; D014161:Transduction, Genetic; D016896:Treatment Outcome
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen