Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
Clin Cancer Res. 2009 Dec 1;15(23):7137-43. doi: 10.1158/1078-0432.CCR-09-1914. Epub 2009 Nov 24.
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.
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.
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.
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.
使用经典方法鉴定次要组织相容性抗原 (mHag) 通常需要复杂的技术、测定和耐心。我们在此描述并验证了一种非繁琐且方便的遗传方法，该方法基于 mHag 合子与 HapMap 单核苷酸多态性基因型的全基因组相关性，可在合理的时间内鉴定出具有临床相关性的 mHag。
使用这种方法，我们寻找了一种由 HLA-DRB1*1501 限制的 T 细胞克隆识别的 mHag，该克隆是从一名多发性骨髓瘤患者中分离出来的，该患者在与急性移植物抗宿主病 3 级相关的强烈移植物抗肿瘤效应期间。
在 3 个月的时间里，我们确定了 54 名 HapMap 个体的 mHag 表型，推断了 20 名个体的合子状态，通过合子-基因型相关性分析定义了 mHag 基因座，测试了来自该基因座的潜在 mHag 肽，最后表明 mHag 是由 SLC19A1 基因中的非同义单核苷酸多态性的精氨酸 (R) 等位基因编码的。
我们得出结论，这种强大且方便的策略为快速鉴定与移植物抗肿瘤效应和移植物抗宿主病相关的 mHag 提供了一个广泛适用的平台。
