Gjertsen H A, Lundin K E, Sollid L M, Eriksen J A, Thorsby E
Institute of Transplantation Immunology, National Hospital, Oslo, Norway.
Hum Immunol. 1994 Apr;39(4):243-52. doi: 10.1016/0198-8859(94)90267-4.
CD is unique among the HLA-associated diseases since (a) the disease-promoting agent (gliadin) is known and (b) the disease is precipitated mainly in individuals carrying a particular cis- or trans-encoded HLA-DQ heterodimer; i.e., DQ(alpha 10501, beta 10201). Further, a preponderance of gliadin-specific T cells derived from the small intestinal mucosa of CD patients are restricted by this DQ heterodimer. T-cell recognition of gliadin peptides presented by the DQ(alpha 10501, beta 10201) heterodimer may thus be of importance in CD. Here we report that a T-cell clone from a patient with CD recognizes a synthetic alpha-gliadin peptide, when presented by the cis- or trans-encoded CD-associated DQ(alpha 10501, beta 10201) heterodimer. The minimal peptide recognized by the T-cell clone corresponds to residues 31-47 of alpha-gliadin, which is included in the part of alpha-gliadin previously shown to have disease-promoting activity. When testing analogue peptides derived from other alpha-gliadin sequences, one peptide differing by one amino acid was recognized by the T-cell clone, whereas the other peptide differing by two amino acids was not recognized. Our findings demonstrate that the CD-associated DQ(alpha 10501, beta 10201) heterodimer may serve as an antigen-presenting molecule to T cells for certain gliadin peptides.
在与HLA相关的疾病中，乳糜泻（CD）独具特色，原因如下：（a）促病因子（麦醇溶蛋白）已知；（b）该疾病主要在携带特定顺式或反式编码的HLA - DQ异二聚体的个体中引发，即DQ（α1 * 0501，β1 * 0201）。此外，源自CD患者小肠黏膜的大量麦醇溶蛋白特异性T细胞受此DQ异二聚体限制。因此，DQ（α1 * 0501，β1 * 0201）异二聚体对麦醇溶蛋白肽的T细胞识别在CD中可能具有重要意义。在此我们报告，来自一名CD患者的T细胞克隆在由顺式或反式编码的与CD相关的DQ（α1 * 0501，β1 * 0201）异二聚体呈递时，可识别一种合成的α - 麦醇溶蛋白肽。该T细胞克隆识别的最小肽对应于α - 麦醇溶蛋白的31 - 47位氨基酸残基，这部分α - 麦醇溶蛋白先前已显示具有促病活性。在测试源自其他α - 麦醇溶蛋白序列的类似肽时，一个相差一个氨基酸的肽被T细胞克隆识别，而另一个相差两个氨基酸的肽未被识别。我们的研究结果表明，与CD相关的DQ（α1 * 0501，β1 * 0201）异二聚体可能作为某些麦醇溶蛋白肽的T细胞抗原呈递分子。
