Chen M, Xu X C, Wu W S, Mohanakumar T
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Transplantation. 1999 Aug 27;68(4):586-9. doi: 10.1097/00007890-199908270-00026.
The human xenoreactive T-cell receptor (TCR) repertoire is not well documented. The aim of this study was to analyze the TCR repertoire in human anti-porcine xenoresponses.
Peripheral blood lymphocytes (PBLs) from healthy donors were used to generate human T-cell lines against two different haplotypes of inbred Yucatan miniature swine (y/y and z/z). The variable region of TCR beta-chain (Vbeta) gene usage was determined by fluorescence CDR3 spectrotyping.
TCR Vbeta usage of an established human antiporcine T-cell line analyzed at weeks 5, 7, and 9 showed a sequential increase in Vbeta 1, 2, 6.2, 11, and 19 as compared to unprimed peripheral blood lymphocytes, whereas the usage of other Vbetas decreased. The selection of limited Vbeta genes correlated with the sequential increase in the specific lysis of the T-cell line, suggesting a non-random clonal selection and expansion of T-cell clones that recognized porcine targets. Different Vbeta restriction was found using the same peripheral blood lymphocytes against a different haplotype of swine, indicating this selection of Vbeta gene was swine leukocyte antigen-dependent.
There is restricted TCR Vbeta usage in the human anti-porcine response, suggesting that a limited number of xenogeneic epitopes are recognized by human T cells. The selection of particular TCR Vbeta clonotypes depends on the swine leukocyte antigen background.
人类异种反应性T细胞受体（TCR）库尚未得到充分记录。本研究的目的是分析人类抗猪异种反应中的TCR库。
使用健康供体的外周血淋巴细胞（PBL）来生成针对两种不同单倍型的近交尤卡坦小型猪（y/y和z/z）的人类T细胞系。通过荧光CDR3光谱分型确定TCRβ链（Vβ）基因的可变区使用情况。
在第5、7和9周分析的已建立的人类抗猪T细胞系的TCR Vβ使用情况显示，与未致敏的外周血淋巴细胞相比，Vβ1、2、6.2、11和19的使用情况呈顺序增加，而其他Vβ的使用情况减少。有限的Vβ基因选择与T细胞系特异性裂解的顺序增加相关，表明识别猪靶标的T细胞克隆存在非随机的克隆选择和扩增。使用相同的外周血淋巴细胞针对不同单倍型的猪发现了不同的Vβ限制，表明这种Vβ基因的选择是猪白细胞抗原依赖性的。
在人类抗猪反应中TCR Vβ的使用受到限制，表明人类T细胞识别的异种抗原表位数量有限。特定TCR Vβ克隆型的选择取决于猪白细胞抗原背景。
