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

Robbert M. Spaapen, R. A L De Kort, Kelly Van Den Oudenalder, Maureen Van Elk, Andries C. Bloem, Henk M. Lokhorst, Tuna Mutis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)7137-7143
Number of pages7
JournalClinical Cancer Research
Volume15
Issue number23
DOIs
Publication statusPublished - 1 Dec 2009

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