PURPOSE: Identification of minor histocompatibility antigens (mHag) with classic methods often requires sophisticated technologies, determination, and patience. We here describe and validate a nonlaborious and convenient genetic approach, based on genome-wide correlations of mHag zygosities with HapMap single-nucleotide polymorphism genotypes, to identify clinical relevant mHags within a reasonable time frame. EXPERIMENTAL DESIGN: Using this approach, we sought for the mHag recognized by a HLA-DRB1*1501-restricted T-cell clone, isolated from a multiple myeloma patient during a strong graft-versus-tumor effect associated with acute graft-versus-host disease grade 3. RESULTS: In a period of 3 months, we determined the mHag phenotype of 54 HapMap individuals, deduced the zygosity of 20 individuals, defined the mHag locus by zygosity-genotype correlation analyses, tested the putative mHag peptides from this locus, and finally showed that the mHag is encoded by the arginine (R) allele of a nonsynonymous single-nucleotide polymorphism in the SLC19A1 gene. CONCLUSIONS: We conclude that this powerful and convenient strategy offers a broadly accessible platform toward rapid identification of mHags associated with graft-versus-tumor effect and graft-versus-host disease.
PURPOSE: Identification of minor histocompatibility antigens (mHag) with classic methods often requires sophisticated technologies, determination, and patience. We here describe and validate a nonlaborious and convenient genetic approach, based on genome-wide correlations of mHag zygosities with HapMap single-nucleotide polymorphism genotypes, to identify clinical relevant mHags within a reasonable time frame. EXPERIMENTAL DESIGN: Using this approach, we sought for the mHag recognized by a HLA-DRB1*1501-restricted T-cell clone, isolated from a multiple myelomapatient during a strong graft-versus-tumor effect associated with acute graft-versus-host disease grade 3. RESULTS: In a period of 3 months, we determined the mHag phenotype of 54 HapMap individuals, deduced the zygosity of 20 individuals, defined the mHag locus by zygosity-genotype correlation analyses, tested the putative mHag peptides from this locus, and finally showed that the mHag is encoded by the arginine (R) allele of a nonsynonymous single-nucleotide polymorphism in the SLC19A1 gene. CONCLUSIONS: We conclude that this powerful and convenient strategy offers a broadly accessible platform toward rapid identification of mHags associated with graft-versus-tumor effect and graft-versus-host disease.
Authors: Rimke Oostvogels; Henk M Lokhorst; Monique C Minnema; Maureen van Elk; Kelly van den Oudenalder; Eric Spierings; Tuna Mutis; Robbert M Spaapen Journal: Haematologica Date: 2014-08-22 Impact factor: 9.941
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Authors: T Yamamura; J Hikita; M Bleakley; T Hirosawa; A Sato-Otsubo; H Torikai; T Hamajima; Y Nannya; A Demachi-Okamura; E Maruya; H Saji; Y Yamamoto; T Takahashi; N Emi; Y Morishima; Y Kodera; K Kuzushima; S R Riddell; S Ogawa; Y Akatsuka Journal: Tissue Antigens Date: 2012-05-08
Authors: Susan Nicholls; Ricardo Pong-Wong; Louisa Mitchard; Ross Harley; Alan Archibald; Andrew Dick; Michael Bailey Journal: PLoS One Date: 2016-03-24 Impact factor: 3.240
Authors: R Oostvogels; M C Minnema; M van Elk; R M Spaapen; G D te Raa; B Giovannone; A Buijs; D van Baarle; A P Kater; M Griffioen; E Spierings; H M Lokhorst; T Mutis Journal: Leukemia Date: 2012-10-01 Impact factor: 11.528