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Clin Cancer Res. 2009 Dec 1;15(23):7137-43. doi: 10.1158/1078-0432.CCR-09-1914. Epub 2009 Nov 24.

Rapid identification of clinical relevant minor histocompatibility antigens via genome-wide zygosity-genotype correlation analysis.

Author information

1
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.

Abstract

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.

PMID:
19934307
DOI:
10.1158/1078-0432.CCR-09-1914
[Indexed for MEDLINE]
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