Since the beginning of life, every multicellular organism appeared to have a complex innate immune system although the adaptive immune system, centred on lymphocytes bearing antigen receptors generated by somatic recombination, arose in jawed fish approximately 500 million years ago. The major histocompatibility complex MHC, named the Human leucocyte antigen (HLA) system in humans, represents a vital function structure in the organism by presenting pathogen‐derived peptides to T cells as the main initial step of the adaptive immune response. The huge level of polymorphism observed in HLA genes definitely reflects selection, favouring heterozygosity at the individual or population level, in a pathogen‐rich environment, although many are located in introns or in exons that do not code for the antigen‐biding site of the HLA. Over the past three decades, the extent of allelic diversity at HLA loci has been well characterized using high‐resolution HLA‐DNA typing and the number of new HLA alleles, produced through next‐generation sequencing methods, is even more rapidly increasing. The level of the HLA system polymorphism represents an obstacle to the search of potential compatible donors for patients affected by haematological disease proposed for a hematopoietic stem cell transplant (HSCT). Data reported in literature clearly show that antigenic and/or allelic mismatches between related or unrelated donors and patients influences the successful HSCT outcome. However, the recent development of the new transplant strategy based on the choice of haploidentical donors for HSCT is questioning the role of HLA compatibility, since the great HLA disparities present do not worsen the overall clinical outcome. Nowadays, NGS has contributed to define at allelic levels the HLA polymorphism and solve potential ambiguities. However, HLA functions and tissue typing probably need to be further investigated in the next future, to understand the reasons why in haploidentical transplants the presence of a whole mismatch haplotype between donors and recipients, both the survival rate and the incidence of acute GvHD or graft rejection are similar to those reported for unrelated HSCTs.

中文翻译：

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人类白细胞抗原多样性：逃避感染的生物礼物，不再是半相合造血干细胞移植的障碍

自生命开始以来，每个多细胞生物似乎都有一个复杂的先天免疫系统，尽管以携带体细胞重组产生的抗原受体的淋巴细胞为中心的适应性免疫系统大约在 5 亿年前出现在有颚鱼中。主要组织相容性复合体 MHC，称为人类人类白细胞抗原 (HLA) 系统，通过将病原体衍生肽呈递给 T 细胞作为适应性免疫反应的主要初始步骤，代表了生物体中的重要功能结构。在富含病原体的环境中，HLA 基因中观察到的大量多态性肯定反映了选择，有利于个体或群体水平的杂合性，尽管许多位于不编码抗原结合位点的内含子或外显子中。 HLA。在过去的 30 年里，HLA 基因座的等位基因多样性的程度已经使用高分辨率 HLA-DNA 分型得到了很好的表征，并且通过下一代测序方法产生的新 HLA 等位基因的数量正在更快地增加。HLA 系统多态性的水平代表了为造血干细胞移植 (HSCT) 受血液病影响的患者寻找潜在相容供体的障碍。文献中报告的数据清楚地表明，相关或无关供体和患者之间的抗原和/或等位基因错配会影响成功的 HSCT 结果。然而，最近基于 HSCT 半相合供体选择的新移植策略的发展正在质疑 HLA 相容性的作用，因为存在的巨大 HLA 差异不会使整体临床结果恶化。如今，NGS 已在等位基因水平定义 HLA 多态性并解决潜在的歧义。然而，未来可能需要进一步研究 HLA 功能和组织分型，以了解为什么在单倍体移植中供体和受体之间存在完全错配的单倍型，存活率和急性 GvHD 或移植物的发生率排斥反应与不相关 HSCT 报告的排斥反应相似。