HLA-DPBI Mismatching Results in the Generation of a Full Repertoire of HLA-DPBI-Specific CD4(+) T Cell Responses Showing Immunogenicity of all HLA-DPBI Alleles

Abstract

Clinical studies have indicated that HLA-DPBI functions as a classical transplantation antigen in allogeneic stem cell transplantation. Mismatching for HLA-DPBI was associated with an increased risk of graft-versus-host disease (GVHD), but also a decreased risk of disease relapse. However, specific HLA-DPBI mismatches were associated with poor clinical outcome. It was suggested that this unfavorable effect was caused by a difference in immunogenicity between HLA-DPBI alleles. To analyze whether immunogenicity of HLA-DPBI mismatches could be predicted based on the presence or absence of specific amino acid sequences we developed a model to generate allo-HLA-DPBI responses in vitro. We tested in total 48 different stimulator/responder combinations by stimulating CD4(+) T cells from 5 HLA-DPBI homozygous individuals with the same antigen-presenting cells transduced with different allo-HLA-DPBI molecules. HLA-DPBI molecules used for stimulation comprised 76% to 99% of HLA-DPBI molecules present in different ethnic populations. We show that all HLA-DPBI mismatches as defined by allele typing resulted in high-frequency immune responses. Furthermore, we show that crossrecognition of different HLA-DPBI molecules is a broadly observed phenomenon. We confirm previously described patterns in crossrecognition, and demonstrate that a high degree in similarity between HLA-DPBI molecules is predictive for crossrecognition, but not for immunogenicity. Biol Blood Marrow Transplant 16: 1282-1292 (2010) (C) 2010 American Society for Blood and Marrow Tramplantation