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T细胞对由两种不同HLA单倍型共同存在所产生的II类产物的识别。

T-cell recognition of class II products that result from the combined presence of two different HLA haplotypes.

作者信息

Schroeijers W E, de Koster H S, Verduyn W, Schreuder G M, Termijtelen A

机构信息

Department of Immunohaematology, University Hospital Leiden, The Netherlands.

出版信息

Hum Immunol. 1992 Apr;33(4):229-34. doi: 10.1016/0198-8859(92)90329-l.

DOI:10.1016/0198-8859(92)90329-l
PMID:1639629
Abstract

To analyze DR2 haplotypes as recognized by alloreactive T cells, lymphocytes from a DR7; DQw2 homozygous donor were cocultured with irradiated lymphocytes that were DRw15, DR7; DQw6, DQw2 heterozygous. In this report, we focus on two HLA-DQ-specific T-cell clones obtained from this priming. These two clones (c3518 and c3523) responded to the positive control (original stimulator) and five of 66 panel donors. Three of these donors typed DRw15, DR7; DQw6, DQw2, as did the positive control. One stimulatory donor typed DRw15, DR7; DQw6, DQw9 and one stimulatory donor typed DRw14, DR7; DQw5, DQw2. Oligonucleotide typing revealed that recognition by the clones depended on the simultaneous presence of the DQB10602 gene on one haplotype and DRB10701 or DQA0201 on the other. The hypothesis that c3518 and c3523 recognize an HLA class II product that results from the combination of two different HLA haplotypes was further confirmed in family studies. In three families, it was shown that the DRw15, DR7; DQw6, (DQw2 or DQw9)-positive individuals were recognized, whereas the cells carrying either DRw15; DQw6, DR7; DQw2, or DR7; DQw9 were nonstimulatory. Our results can be explained in two ways: (a) the T cells recognize a class II dimer that results from trans-complementation of DQA10101 and DQB1*0602, and (2) the T cells recognize a DR7-derived peptide that is presented by DQw6.

摘要

为分析同种反应性T细胞识别的DR2单倍型,将来自DR7; DQw2纯合供体的淋巴细胞与经照射的DRw15、DR7; DQw6、DQw2杂合淋巴细胞共培养。在本报告中,我们重点关注从该启动过程中获得的两个HLA - DQ特异性T细胞克隆。这两个克隆(c3518和c3523)对阳性对照(原始刺激细胞)和66个供体库中的5个有反应。其中3个供体的分型为DRw15、DR7; DQw6、DQw2,与阳性对照相同。一个刺激供体的分型为DRw15、DR7; DQw6、DQw9,另一个刺激供体的分型为DRw14、DR7; DQw5、DQw2。寡核苷酸分型显示,克隆的识别依赖于一个单倍型上同时存在DQB10602基因,以及另一个单倍型上存在DRB10701或DQA0201。c3518和c3523识别由两种不同HLA单倍型组合产生的HLA II类产物这一假说在家族研究中得到了进一步证实。在三个家族中,结果显示DRw15、DR7; DQw6、(DQw2或DQw9)阳性个体可被识别,而携带DRw15; DQw6、DR7; DQw2或DR7; DQw9的细胞无刺激作用。我们的结果可以用两种方式解释:(a) T细胞识别由DQA10101和DQB1*0602反式互补产生的II类二聚体,以及(2) T细胞识别由DQw6呈递的DR7衍生肽。

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引用本文的文献

1
The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families.人类白细胞抗原II类基因在胰岛素依赖型糖尿病中的作用:对180个高加索多重家庭的分子分析
Am J Hum Genet. 1996 Nov;59(5):1134-48.