From the HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Hematology and Bone Marrow Transplantation Unit, Cancer Immunotherapy and Gene Therapy Program, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Istituto Scientifico H. S. Raffaele, Milan, Italy; Immunogenetics Laboratory, Unit of Clinical Epidemiology and Trials, IRCCS National Institute for Cancer Research, Genoa, Italy; Department of Hematology, Imperial College, London, United Kingdom; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Department of Pediatric Hematology-Oncology, IRCCS Policlinico S. Matteo, Pavia, Italy; HLA Tissue Typing Laboratory, Immunohematology and Transfusion Medicine Service, Institute of Hematology and Medical Oncology, University of Bologna, Ospedale S. Orsola-Malpighi, Bologna, Italy; Department of Pediatric Hematology-Oncology, IRCCS G. Gaslini, Genoa, Italy; Department of Hematology, Ospedale San Martino, Genoa, Italy; and Department of Oncology, Biology and Genetics, University of Genoa, Genoa, Italy.
The importance of HLA-DPB1 matching for the outcome of allogeneic hematologic stem cell (HSC) transplantation is controversial. We have previously identified HLA-DPB1*0901 as a target of cytotoxic T cells mediating in vivo rejection of an HSC allograft. Here we show that HLA-DPB1*0901 encodes a T-cell epitope shared by a subset of DPB1 alleles that determines nonpermissive mismatches for HSC transplantation. Several T-cell clones obtained from the patient at the time of rejection showed HLA-DP restricted recognition of allogeneic targets expressing HLA-DPB1*0901, *1001, *1701, *0301, *1401, and *4501, but not other alleles. Based on these findings, we developed an algorithm for prediction of nonpermissive HLA-DPB1 mismatches. Retrospective evaluation of 118 transplantations showed that the presence of nonpermissive HLA-DPB1 mismatches was correlated with significantly increased hazards of acute grade II to IV graft-versus-host disease (HR = 1.87, P = .046) and transplantation-related mortality (HR = 2.69, P = .027) but not relapse (HR = 0.98, P = .939), as compared with the permissive group. There was also a marked but statistically not significant increase in the hazards of overall mortality (HR = 1.64, P = .1). These data suggest that biologic characterization of in vivo alloreactivity can be a tool for definition of clinically relevant nonpermissive HLA mismatches for unrelated HSC transplantation.
Cytolytic T Lymphocytes (CTLs) from HIV-1 Subtype CInfected Indian Patients Recognize CTL Epitopes from a Conserved Immunodominant Region of HIV-1 Gag and Nef
Protective Effect of the HLA-Bw4I80 Epitope and the Killer Cell Immunoglobulin-Like Receptor 3DS1 Gene against the Development of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Infection
Identification and characterization of epitopes of the receptor for hyaluronic acid–mediated motility (RHAMM/CD168) recognized by CD8+ T cells of HLA-A2–positive patients with acute myeloid leukemia
Identification of a transiently exposed Ve-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature
Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro–transcribed MUC1 RNA
Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin
Relationship between Thyroid Peroxidase T Cell Epitope Restriction and Antibody Recognition of the Autoantibody Immunodominant Region in Human Leukocyte Antigen DR3 Transgenic Mice
New Insights into the Conformational Dominant Epitopes on Thyroid Peroxidase Recognized by Human Autoantibodies
Identification of Novel HLA-A0201–Restricted Epitopes in Recent-Onset Type 1 Diabetic Subjects and Antibody-Positive Relatives
Recognition of HLA Class I–Restricted -Cell Epitopes in Type 1 Diabetes