title: Identification of minor histocompatibility antigens based on the 1000 Genomes Project.
abstract: Minor histocompatibility antigens are highly immunogeneic polymorphic peptides playing crucial roles in the clinical outcome of HLA-identical allogeneic stem cell transplantation. Although the introduction of genome-wide association-based strategies significantly has accelerated the identification of minor histocompatibility antigens over the past years, more efficient, rapid and robust identification techniques are required for a better understanding of the immunobiology of minor histocompatibility antigens and for their optimal clinical application in the treatment of hematologic malignancies. To develop a strategy that can overcome the drawbacks of all earlier strategies, we now integrated our previously developed genetic correlation analysis methodology with the comprehensive genomic databases from the 1000 Genomes Project. We show that the data set of the 1000 Genomes Project is suitable to identify all of the previously known minor histocompatibility antigens. Moreover, we demonstrate the power of this novel approach by the identification of the new HLA-DP4 restricted minor histocompatibility antigen UTDP4-1, which despite extensive efforts could not be identified using any of the previously developed biochemical, molecular biological or genetic strategies. The 1000 Genomes Project-based identification of minor histocompatibility antigens thus represents a very convenient and robust method for the identification of new targets for cancer therapy after allogeneic stem cell transplantation.
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht; Department of Hematology, University Medical Center Utrecht, Utrecht;
authors.forename: Rimke
authors.initials: R
authors.lastname: Oostvogels
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht; Department of Hematology, VU University Medical Center, Amsterdam;
authors.forename: Henk M
authors.initials: HM
authors.lastname: Lokhorst
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht;
authors.forename: Monique C
authors.initials: MC
authors.lastname: Minnema
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht;
authors.forename: Maureen
authors.initials: M
authors.lastname: van Elk
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht;
authors.forename: Kelly
authors.initials: K
authors.lastname: van den Oudenalder
authors.affiliation: Department of Immunology, University Medical Center Utrecht, Utrecht;
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht; Department of Hematology, VU University Medical Center, Amsterdam; t.mutis@umcutrecht.nl.
authors.forename: Tuna
authors.initials: T
authors.lastname: Mutis
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht; Department of Immunopathology, Sanquin Research, Amsterdam; Department of Cell Biology II, The Netherlands Cancer Institute, Amsterdam; Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, the Netherlands.
authors.forename: Robbert M
authors.initials: RM
authors.lastname: Spaapen
mesh_terms: D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D019337:Hematologic Neoplasms / Q000235:genetics* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D046228:Microarray Analysis; D015778:Minor Histocompatibility Antigens / Q000145:classification* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014184:Transplantation, Homologous
chemical_list: D015778:Minor Histocompatibility Antigens