SHARED T-CELL RECOGNITION SITES ON HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN CLASS-II MOLECULES OF PATIENTS WITH SEROPOSITIVE RHEUMATOID-ARTHRITIS
SHARED T-CELL RECOGNITION SITES ON HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGEN CLASS-II MOLECULES OF PATIENTS WITH SEROPOSITIVE RHEUMATOID-ARTHRITIS
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DOI：
10.1172/jci112358
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发表时间：
1986-03-01
影响因子：
15.9
通讯作者：
FATHMAN, CG
中科院分区：
文献类型：
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作者：
GORONZY, J;WEYAND, CM;FATHMAN, CG
成人和青少年患者中血清阳性的类风湿性关节炎(RA)与血清标志物HLA-DR4有关。这种关联是不完整的；大约三分之一的患者缺乏与疾病相关的人类白细胞抗原-DR4单倍型。第二类分子的主要生物学功能是限制T淋巴细胞对抗原的识别。因此，我们测试了一种假设，即血清阳性RA患者共享未知抗原的T细胞识别位点，并且这种T细胞“表位”不能通过传统的血清学分型来识别。我们通过刺激正常捐献者的外周血淋巴细胞来产生同种异体反应的人类T细胞克隆，以对抗来自血清阳性的青少年RA患者的淋巴母细胞系。一组仅识别纯合子分型细胞上的HLA-Dw14细胞的克隆被用来分析血清阳性的成年RA患者的II类分子。通过使用单抗的抑制研究，不同克隆识别的表位可以进一步表征，并分配给DR或DQ编码的细胞表面产物。通过使用四个不同的克隆，可以在所有血清阳性的类风湿患者身上识别出与Dw14相关的T细胞表位，这些患者的类型都是HLA-DR4阳性，也可以识别所有测试的8名DR4阴性患者的Dw14相关T细胞表位。大约一半的非类风湿DR4阳性供者携带这些克隆识别的一个或多个决定因素；这些同种决定因素在DR4阴性的非类风湿患者中的表达是罕见的(<；10%)。因此，同种异体反应性人类T细胞克隆是一种强大的工具，可以用来定义传统分型无法识别的II类分子上的T细胞识别位点。利用表达在Dw14纯合子分型系上的具有决定簇特异性的T细胞克隆，我们能够证明所有血清阳性RA患者的细胞上有共同的表位，无论他们的人类白细胞抗原-D或人类白细胞抗原-DR类型。这些数据表明，类风湿关节炎患者的主要组织相容性复合体II类抗原可能比不完全的人类白细胞抗原-DR4相关性更具同质性。
Seropositive rheumatoid arthritis (RA) in adult and juvenile patients is associated with the serologic marker HLA-DR4. This association is incomplete; about one-third of the patients lack the disease-associated HLA-DR4 haplotype. The main biological function of class II molecules is to restrict the recognition of antigen by T lymphocytes. We therefore tested the hypothesis that patients with seropositive RA share T cell recognition sites for an unknown antigen and that such T cell "epitopes" are not identified by conventional serologic typing. We generated alloreactive human T cell clones by stimulating peripheral blood lymphocytes of normal donors against a lymphoblastoid cell line from a juvenile patient with seropositive RA. A panel of clones that recognized only HLA-Dw14 cells on a panel of homozygous typing cells was used to analyze class II molecules of adult patients with seropositive RA. By inhibition studies using monoclonal antibodies, the epitopes recognized by the different clones could be further characterized and assigned either to DR- or to DQ-encoded cell surface products. By using four different clones, it was possible to identify Dw14-associated T cell epitopes on all seropositive rheumatoid patients tested who typed HLA-DR4-positive and also on all eight DR4-negative patients tested. Approximately one-half of nonrheumatoid DR4-positive donors carried one or more determinants recognized by these clones; the expression of these allodeterminants in DR4-negative nonrheumatoid patients was rare (< 10%). Thus, alloreactive human T cell clones are powerful tools to define T cell recognition sites on class II molecules that are not identified by conventional typing. Using T cell clones with specificities for determinants expressed on Dw14 homozygous typing lines, we were able to demonstrate shared epitopes on cells of all patients tested with seropositive RA irrespective of their HLA-D or HLA-DR type. These data suggest that major histocompatibility complex class II antigens of RA patients might be much more homogeneous than demonstrated by the incomplete HLA-DR4 association.