HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis.
HLA-DR4-IE chimeric class II transgenic, murine class II-deficient mice are susceptible to experimental allergic encephalomyelitis.
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DOI：
10.1084/jem.183.6.2635
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发表时间：
1996-06-01
期刊：
影响因子：
--
通讯作者：
Nagy ZA
中科院分区：
文献类型：
--
作者：
Ito K;Bian HJ;Molina M;Han J;Magram J;Saar E;Belunis C;Bolin DR;Arceo R;Campbell R;Falcioni F;Vidović D;Hammer J;Nagy ZA
为了研究hla - dr相关自身免疫性疾病的发生，我们培育了HLA-DRA-IE α和HLA-DRB1*0401-IE β嵌合基因的转基因（Tg）小鼠。转基因编码的蛋白由HLA-DRA和HLA-DRB1*0401分子的抗原结合结构域和IE(d)- α和IE(d)- β链的抗原结合结构域组成。嵌合分子与HLA-DRB1*0401分子具有相同的抗原结合特异性，并具有向T细胞呈递抗原的功能。将Tg小鼠与MHC II类缺陷（IA β -, IE α -）小鼠回交，以消除内源性MHC II类基因对自身免疫性疾病发展的任何影响。正如预期的那样，IA α β或IE α β分子在Tg小鼠中未表达。此外，通过流式细胞术分析，在一些Tg小鼠细胞系中未检测到内源性IE β与HLA-DRA-IE α相关的细胞表面表达。HLA-DRA-IE α /HLA-DRB1*0401-IE β分子挽救了MHC ii类缺陷小鼠CD4+ T细胞的发育，但表达V β 5、V β 11和V β 12的T细胞被特异性删除。用被认为是HLA-DR4个体免疫优势表位的髓鞘碱性蛋白（MBP） 87-106和蛋白脂质蛋白（PLP） 175-192肽段免疫Tg小鼠。PLP175-192引起Tg小鼠淋巴结T细胞的强烈增殖反应，引起中枢神经系统白质炎症病变和实验性变应性脑脊髓炎（EAE）症状。用MBP87- 106免疫可引起非常弱的增殖T细胞反应，并引起轻度EAE。用PLP175-192或MBP87-106免疫的非tg小鼠未发生EAE。这些结果表明，人类MHC II类结合位点单独可以赋予实验诱导的小鼠自身免疫性疾病的易感性。
To investigate the development of HLA-DR-associated autoimmune diseases, we generated transgenic (Tg) mice with HLA-DRA-IE alpha and HLA-DRB1*0401-IE beta chimeric genes. The transgene-encoded proteins consisted of antigen-binding domains from HLA-DRA and HLA-DRB1*0401 molecules and the remaining domains from the IE(d)-alpha and IE(d)-beta chains. The chimeric molecules showed the same antigen-binding specificity as HLA-DRB1*0401 molecules, and were functional in presenting antigens to T cells. The Tg mice were backcrossed to MHC class II-deficient (IA beta-, IE alpha-) mice to eliminate any effect of endogenous MHC class II genes on the development of autoimmune diseases. As expected, IA alpha beta or IE alpha beta molecules were not expressed in Tg mice. Moreover, cell-surface expression of endogenous IE beta associated with HLA-DRA-IE alpha was not detectable in several Tg mouse lines by flow cytometric analysis. The HLA-DRA-IE alpha/HLA-DRB1*0401-IE beta molecules rescued the development of CD4+ T cells in MHC class II-deficient mice, but T cells expressing V beta 5, V beta 11, and V beta 12 were specifically deleted. Tg mice were immunized with peptides, myelin basic protein (MBP) 87-106 and proteolipid protein (PLP) 175-192, that are considered to be immunodominant epitopes in HLA-DR4 individuals. PLP175-192 provoked a strong proliferative response of lymph node T cells from Tg mice, and caused inflammatory lesions in white matter of the CNS and symptoms of experimental allergic encephalomyelitis (EAE). Immunization with MBP87- 106 elicited a very weak proliferative T cell response and caused mild EAE. Non-Tg mice immunized with either PLP175-192 or MBP87-106 did not develop EAE. These results demonstrated that a human MHC class II binding site alone can confer susceptibility to an experimentally induced murine autoimmune disease.
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影响因子：
56.9
作者：
GRUSBY, MJ;JOHNSON, RS;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
DOI：
10.1084/jem.181.3.867
发表时间：
1995-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Altmann DM;Douek DC;Frater AJ;Hetherington CM;Inoko H;Elliott JI
通讯作者：
Elliott JI
影响因子：
64.8
作者：
CAMMAROTA, G;SCHEIRLE, A;SINIGAGLIA, F
通讯作者：
SINIGAGLIA, F
DOI：
10.1073/pnas.80.18.5520
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
SAITO, H;MAKI, RA;TONEGAWA, S
通讯作者：
TONEGAWA, S
DOI：
10.1073/pnas.87.20.7968
发表时间：
1990-10-01
影响因子：
11.1
作者：
PETTE, M;FUJITA, K;WEKERLE, H
通讯作者：
WEKERLE, H