Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States.
Front Immunol. 2021 Nov 18;12:782152. doi: 10.3389/fimmu.2021.782152. eCollection 2021.
Minor histocompatibility antigens (mHAg) composed of peptides presented by HLA molecules can cause immune responses involved in graft-versus-host disease (GVHD) and graft-versus-leukemia effects after allogeneic hematopoietic cell transplantation (HCT). The current study was designed to identify individual graft-versus-host genomic mismatches associated with altered risks of acute or chronic GVHD or relapse after HCT between HLA-genotypically identical siblings. Our results demonstrate that in allogeneic HCT between a pair of HLA-identical siblings, a mHAg manifests as a set of peptides originating from annotated proteins and non-annotated open reading frames, which i) are encoded by a group of highly associated recipient genomic mismatches, ii) bind to HLA allotypes in the recipient, and iii) evoke a donor immune response. Attribution of the immune response and consequent clinical outcomes to individual peptide components within this set will likely differ from patient to patient according to their HLA types.
次要组织相容性抗原（mHAg）由 HLA 分子呈递的肽组成，可引起移植物抗宿主病（GVHD）和同种异体造血细胞移植（HCT）后移植物抗白血病效应的免疫反应。本研究旨在确定与 HLA 基因分型相同的兄弟姐妹之间 HCT 后急性或慢性 GVHD 或复发风险改变相关的个体移植物抗宿主基因组错配。我们的研究结果表明，在 HLA 基因分型相同的一对兄弟姐妹之间的异基因 HCT 中，mHAg 表现为一组源自注释蛋白和非注释开放阅读框的肽，这些肽：i）由一组高度相关的受者基因组错配编码；ii）与受者中的 HLA 同种型结合；iii）引发供者免疫反应。根据患者的 HLA 类型，将免疫反应和随之而来的临床结果归因于该组内的单个肽成分可能会有所不同。
