Public and private V beta T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice.
Public and private V beta T cell receptor repertoires against hen egg white lysozyme (HEL) in nontransgenic versus HEL transgenic mice.
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DOI：
10.1084/jem.180.3.861
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发表时间：
1994-09-01
影响因子：
15.3
通讯作者：
Kourilsky, Philippe
中科院分区：
文献类型：
--
作者：
Cibotti, Ricardo;Cabaniols, Jean-Pierre;Pannetier, Christophe;Delarbre, Christiane;Vergnon, Isabelle;Kanellopoulos, Jean M.;Kourilsky, Philippe
我们以前已经产生了一个转基因小鼠系的鸡蛋溶菌酶（HEL），一个实验模型，用于分析耐受性的自我抗原在肽水平。我们现在已经表征了HEL血液水平低于2ng/ml的转基因小鼠，其中观察到对HEL及其免疫显性肽的显著T细胞增殖反应。选择这种HEL-low转基因模型是因为它模拟了生理条件，其中识别以非常低水平表达的自身组分的自身反应性T淋巴细胞持续存在而不诱导耐受性的破坏。此外，在H-2d小鼠中，HEL特异性T淋巴细胞由单个免疫显性区域触发，使我们能够分别将转基因和非转基因动物的HEL-specific T细胞V β库与自身或外源肽进行比较。我们发现，在所有非转基因小鼠中，在对HEL的反应中发现了V β 8.2-D β 1-J β 1.5重排，而在HEL-low转基因动物中不存在这种V β限制性反应。在核苷酸水平上，这种重排的结果从修剪的基因组片段在VDJ或DJ加入，没有N添加，这表明显性重排选择早期在胎儿或新生儿的生命，在末端脱氧核苷酸转移酶的表达。在HEL-low转基因小鼠中，没有发现显性重排作为在正常小鼠中观察到的重排的替代。相反，每个转基因动物在其对免疫显性HEL肽的应答中使用不同的V β-J β组合。在非转基因小鼠中，除了显性的V β 8.2-D β 1-J β 1.5组合外，还发现了在每只动物中不同的次要V β谱系，并且与单个转基因小鼠所使用的重排不同。这些发现表明，T细胞对免疫显性肽的反应涉及在所有动物中发现的“公共”V β库和对每个个体特异的“私人”V β库。
We have previously produced a transgenic mouse line for hen egg lysozyme (HEL), an experimental model for analyzing tolerance to self- antigens at the peptide level. We have now characterized transgenic mice with HEL blood levels below 2 ng/ml, where significant T cell proliferative responses to HEL and its immunodominant peptide were observed. This HEL-low transgenic model was chosen because it mimics physiological conditions in which autoreactive T lymphocytes, recognizing self-components expressed at very low levels, persist without inducing a break in tolerance. Furthermore, in H-2d mice, HEL- specific T lymphocytes are triggered by a single immunodominant region, allowing us to compare the HEL-specific T cell V beta repertoires of transgenic and nontransgenic animals against a single peptide presented as self or foreign, respectively. We found that a V beta 8.2-D beta 1-J beta 1.5 rearrangement is found in response to HEL in all nontransgenic mice, whereas this V beta-restricted response is absent in HEL-low transgenic animals. At the nucleotide level, this rearrangement results from the trimming of the genomic segments during VDJ or DJ joining, without N additions, suggesting that the dominant rearrangement is selected early during fetal or neonatal life, before the expression of terminal deoxynucleotidyl transferase. In HEL-low transgenic mice, no dominant rearrangements are found as alternatives to the one observed in normal mice. Instead, each transgenic animal uses a different set of V beta-J beta combinations in its response to the immunodominant HEL peptide. In nontransgenic mice, besides the dominant V beta 8.2-D beta 1-J beta 1.5 combination, minor V beta repertoires were found which differed in each animal and were distinct from the rearrangements used by individual transgenic mice. These findings suggest that the T cell response to an immunodominant peptide involves a "public" V beta repertoire found in all animals and a "private" one which is specific to each individual.
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影响因子：
64.8
作者：
ADORINI, L;MULLER, S;NAGY, ZA
通讯作者：
NAGY, ZA
影响因子：
64.8
作者：
KISIELOW, P;TEH, HS;VONBOEHMER, H
通讯作者：
VONBOEHMER, H
DOI：
10.1073/pnas.88.10.4348
发表时间：
1991-05-01
影响因子：
11.1
作者：
MILICH, DR;MCLACHLAN, A;JONES, JE
通讯作者：
JONES, JE
DOI：
10.1073/pnas.87.17.6599
发表时间：
1990-09-01
影响因子：
11.1
作者：
MILICH, DR;JONES, JE;MCLACHLAN, A
通讯作者：
MCLACHLAN, A
影响因子：
64.8
作者：
KAPPLER, JW;STAERZ, U;MARRACK, PC
通讯作者：
MARRACK, PC