Heterogeneity of antigen specificity between HLA-A02:01 and other frequent Chinese HLA-A2 subtypes detected by a modified autologous lymphocyte-monocyte coculture.
Heterogeneity of antigen specificity between HLA-A02:01 and other frequent Chinese HLA-A2 subtypes detected by a modified autologous lymphocyte-monocyte coculture.
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通过改良的自体淋巴细胞-单核细胞共培养物检测 HLA-A02:01 和其他常见中国 HLA-A2 亚型之间抗原特异性的异质性。
DOI：
10.1016/j.molimm.2019.08.014
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发表时间：
2019
影响因子：
3.6
通讯作者：
Zhuihui Liang
中科院分区：
文献类型：
--
作者：
Jun Chen;Shengjun Lu;Xiufang Weng;Xiongwen Wu;Zhuihui Liang
HLA-A2是所有种族群体中最常见的血清学HLA类型。随着DNA分型技术的发展，已鉴定出800多种HLA-A2亚型，通过对同种异体移植患者的回顾性分析和抗原氨基酸结构的研究，提示HLA-A2亚型之间存在抗原特异性的异质性。然而，在本研究之前，无法在体外研究给定亚型的抗原性或两种给定亚型之间的错配程度。在这里，我们使用了一种改进的自体淋巴细胞-单核细胞共培养方法，以揭示HLA-A2亚型之间的抗原特异性的异质性。用HLA-A2（非A *02：01）淋巴细胞和单核细胞建立共培养物，并通过IgG 1-Fc与FcgRI的高亲和力结合用HLA-A*02：01/IgG 1-Fc融合蛋白（二聚体）包被单核细胞。共培养后的淋巴细胞增殖表明HLA-A*02：01对HLA-A2（non-A*02：01）亚型具有抗原性。在中国人群中最常见的HLA-A2亚型（HLA-A*02：01、-A*02：03、-A*02：06和-A*02：07）中，我们鉴定了来自-A*02：03或-A*02：06但不是-A*02：07个体的T细胞的显著-A*02：01抗原性。我们的研究结果与对涉及有限亚型的同种异体移植患者的回顾性研究一致，表明这种改良的共培养方法为体外研究HLA等位基因亚型的抗原性提供了实用且可靠的手段。
HLA-A2 is the most common serological HLA type among all ethnic groups. Through advances in DNA typing, more than 800 subtypes of HLA-A2 have been identified, and the existence of heterogeneity of antigen specificity among the HLA-A2 subtypes has been suggested by retrospective analyses of allogeneic transplantation patients and by studies of antigen amino acid structure. However, prior to this study, the antigenicity of a given subtype or the mismatch extent between two given subtypes could not be studied in vitro. Here, we used a modified autologous lymphocyte-monocyte coculture method to reveal heterogeneity of antigen specificity among HLA-A2 subtypes. The coculture was set up with HLA-A2 (non-A*02:01) lymphocytes and monocytes, and the monocytes were coated with an HLA-A*02:01/IgG1-Fc fusion protein (dimer) by high-affinity binding of the IgG1-Fc to FcgRI. Lymphocyte proliferation following coculture indicated that HLA-A*02:01 showed antigenicity against the HLA-A2 (non-A*02:01) subtype. Among the most frequent HLA-A2 subtypes in the Chinese population (HLA-A*02:01, -A*02:03, -A*02:06 and -A*02:07), we identified significant -A*02:01 antigenicity for T cells from -A*02:03 or -A*02:06 but not -A*02:07 individuals. Our findings were consistent with retrospective studies of allograft patients with a limited number of involved subtypes, indicating that this modified coculture method provides a practical and reliable means to study the antigenicity of HLA allele subtypes in vitro.