Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2010-11-16
pubmed:abstractText
Patients with malignant diseases can be effectively treated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Polymorphic peptides presented in HLA molecules, the so-called minor histocompatibility antigens (MiHA), play a crucial role in antitumor immunity as targets for alloreactive donor T cells. Identification of multiple MiHAs is essential to understand and manipulate the development of clinical responses after allo-SCT. In this study, CD8+ T-cell clones were isolated from leukemia patients who entered complete remission after allo-SCT, and MiHA-specific T-cell clones were efficiently selected for analysis of recognition of a panel of EBV-transformed B cells positive for the HLA restriction elements of the selected T-cell clones. One million single nucleotide polymorphisms (SNP) were determined in the panel cell lines and investigated for matching with the T-cell recognition data by whole genome association scanning (WGAs). Significant association with 12 genomic regions was found, and detailed analysis of genes located within these genomic regions revealed SNP disparities encoding polymorphic peptides in 10 cases. Differential recognition of patient-type, but not donor-type, peptides validated the identification of these MiHAs. Using tetramers, distinct populations of MiHA-specific CD8+ T cells were detected, demonstrating that our WGAs strategy allows high-throughput discovery of relevant targets in antitumor immunity after allo-SCT.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1538-7445
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 AACR.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9073-83
pubmed:meshHeading
pubmed-meshheading:21062987-Anemia, Refractory, pubmed-meshheading:21062987-CD8-Positive T-Lymphocytes, pubmed-meshheading:21062987-Cells, Cultured, pubmed-meshheading:21062987-Epitopes, T-Lymphocyte, pubmed-meshheading:21062987-Female, pubmed-meshheading:21062987-Genome, Human, pubmed-meshheading:21062987-Genome-Wide Association Study, pubmed-meshheading:21062987-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:21062987-Humans, pubmed-meshheading:21062987-Leukemia, Myelogenous, Chronic, BCR-ABL Positive, pubmed-meshheading:21062987-Male, pubmed-meshheading:21062987-Minor Histocompatibility Antigens, pubmed-meshheading:21062987-Myelodysplastic Syndromes, pubmed-meshheading:21062987-Polymerase Chain Reaction, pubmed-meshheading:21062987-Polymorphism, Single Nucleotide, pubmed-meshheading:21062987-Sequence Analysis, DNA, pubmed-meshheading:21062987-Transplantation, Homologous
pubmed:year
2010
pubmed:articleTitle
High-throughput characterization of 10 new minor histocompatibility antigens by whole genome association scanning.
pubmed:affiliation
Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands. c.a.m.van_bergen@lumc.nl
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't