Xu X C, Naziruddin B, Sasaki H, Smith D M, Mohanakumar T
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Transplantation. 1999 Aug 27;68(4):473-9. doi: 10.1097/00007890-199908270-00005.
The T-cell mediated immune responses play a major role in xenograft rejection. However, the mechanisms behind human T-cell recognition of porcine xenoantigens remain to be elucidated.
Human CD8+ T-cell lines were generated against porcine aortic endothelial cells (PAECs) from y/y and z/z haplotypes of Yucatan inbred swine. T-cell clones were obtained by limiting dilution. The human T-cell receptor (TCR)-swine leukocyte antigen (SLA) class I interaction was characterized.
The human CD8+ T-cell mediated direct recognition of PAECs was SLA haplotype-specific. The haplotype specificity was restricted by the SLA class I allelic polymorphism. To characterize the role of SLA-bound peptides in the human TCR-SLA class I interaction, we stripped peptides from SLA molecules by a brief acid treatment. Using z/z-specific CD8+ T cells as effectors, we demonstrated that the acid-treatment, which stripped SLA molecules of bound peptides, decreased the lysis of PAECs by 72%. Addition of peptides eluted from affinity purified z/z SLA class I molecules, but not from the irrelevant y/y SLA class I, restored the lysis of acid-treated z/z PAECs. In addition, the lysis of a human HLA class I negative cell line, 721.221, transfected with a relevant SLA class I allele derived from the z/z haplotype, was significantly increased with the addition of relevant z/z peptides. These experiments indicated that both SLA class I and bound peptides were required for recognition by human CD8+ T cells. Cloning studies identified two groups of xenoreactive T-cell clones. Group I clones recognized distinct porcine peptides in the context of SLA class I molecules, whereas group II clones recognized human endogenous cross-reactive peptides presented by SLA class I.
Our results demonstrated that, despite the differences in MHC molecules between species, human T-cell recognition of porcine MHC is similar to direct allo-recognition, that is, human TCR recognizes xenogeneic SLA-peptide complexes.
T细胞介导的免疫反应在异种移植排斥中起主要作用。然而，人类T细胞识别猪异种抗原背后的机制仍有待阐明。
针对尤卡坦近交系猪y/y和z/z单倍型的猪主动脉内皮细胞（PAEC）产生人类CD8 + T细胞系。通过有限稀释获得T细胞克隆。对人类T细胞受体（TCR）-猪白细胞抗原（SLA）I类相互作用进行了表征。
人类CD8 + T细胞介导的对PAEC的直接识别具有SLA单倍型特异性。单倍型特异性受SLA I类等位基因多态性的限制。为了表征SLA结合肽在人类TCR-SLA I类相互作用中的作用，我们通过短暂的酸处理从SLA分子中去除肽。使用z/z特异性CD8 + T细胞作为效应细胞，我们证明酸处理去除了SLA分子上结合的肽，使PAEC的裂解减少了72%。添加从亲和纯化的z/z SLA I类分子洗脱的肽，但不是从不相关的y/y SLA I类分子洗脱的肽，恢复了酸处理的z/z PAEC的裂解。此外，用源自z/z单倍型的相关SLA I类等位基因转染的人类HLA I类阴性细胞系721.221，在添加相关的z/z肽后裂解显著增加。这些实验表明，人类CD8 + T细胞识别需要SLA I类和结合的肽。克隆研究鉴定出两组异种反应性T细胞克隆。I组克隆在SLA I类分子的背景下识别不同的猪肽，而II组克隆识别由SLA I类呈递的人类内源性交叉反应肽。
我们的结果表明，尽管物种之间的MHC分子存在差异，但人类T细胞对猪MHC的识别类似于直接同种异体识别，即人类TCR识别异种SLA-肽复合物。
