EXPRESSION OF A TRANSGENIC CLASS-II AB GENE CONFERS SUSCEPTIBILITY TO COLLAGEN-INDUCED ARTHRITIS
EXPRESSION OF A TRANSGENIC CLASS-II AB GENE CONFERS SUSCEPTIBILITY TO COLLAGEN-INDUCED ARTHRITIS
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DOI：
10.1002/eji.1830240736
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发表时间：
1994-07-01
影响因子：
5.4
通讯作者：
HOLMDAHL, R
中科院分区：
文献类型：
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作者：
BRUNSBERG, U;GUSTAFSSON, K;HOLMDAHL, R
主要组织相容性复合体（MHC）II类区域被认为是影响自身免疫性疾病，如类风湿性关节炎。在小鼠中，H-2（q）单倍型与胶原诱导性关节炎的易感性相关，而H-2（p）单倍型则无关。这些单倍型的IIA类分子在β链的第一结构域中仅相差4个氨基酸。为了测试这种差异是否解释了MHC对胶原诱导的关节炎易感性的影响，用改变为类似于Ab（q）基因的Ab（p）基因使H-2（p）小鼠转基因。转基因A（β）链与A（α）（p）链杂交，并通过测试对A（q）限制性T细胞杂交瘤的抗原呈递能力和FACS分析显示其生理表达。这些转基因小鼠对II型胶原蛋白产生了自身免疫反应，也产生了胶原蛋白诱导的关节炎。这些数据明确地表明Ab基因是自身免疫性胶原诱导性关节炎的主要遗传易感性位点。
The major histocompatibility complex (MHC) class II region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H-2(q) haplotype is associated with susceptibility to collagen-induced arthritis, while the H-2(p) haplotype is not. The class II A molecules of these haplotypes differ by only four amino acids in the first domain of the beta chain. To test if this difference accounts for the MHC influence on susceptibility to collagen-induced arthritis, H-2(p) mice were made transgenic with an Ab(p) gene altered to resemble the Ab(q) gene. The transgenic A(beta) chain hybridized with the A(alpha)(p) chain and was shown to be physiologically expressed by testing antigen-presentation capacity to A(q)-restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type II collagen and also collagen-induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen-induced arthritis.