An altered T cell repertoire in MECL-1-deficient mice
An altered T cell repertoire in MECL-1-deficient mice
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DOI：
10.4049/jimmunol.176.11.6665
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Monaco, John J.
中科院分区：
文献类型：
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作者：
Basler, Michael;Moebius, Jacqueline;Monaco, John J.
免疫蛋白酶体亚单位低分子量多肽（LMP）2和LMP 7影响MHC I类分子的Ag呈递。在本研究中，我们研究了第三免疫亚基LMP 10/多催化内肽酶复合物样（MECL）-1（beta 2 i）在MECL-1基因靶向小鼠中的功能。MECL-1（-/-）小鼠中CD 8（+）脾细胞的数量比野生型小鼠低20%。淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染MECL-1（-/-）小鼠后，对LCMV表位GP 276 -286/D-h和NP 205 -212/K-b的细胞毒性T细胞（CTL）反应明显减弱。对GP 276 -286/D-B的弱CTL应答不是由于该表位的产生受损，而是由于GP 276 - 286 D（B）特异性T细胞的前体频率降低。在LCMV感染的MECL-1（-/-）小鼠中，含有GP 276 -286/D-b特异性细胞的TCR-V（beta）10（+）T细胞的扩增减少。总之，我们的数据揭示了MECL-1在共同决定抗病毒CTL应答的T细胞库中的体内功能。
Immunoproteasome subunits low-molecular mass polypeptide (LMP)2 and LMP7 affect Ag presentation by MHC class I molecules. In the present study, we investigated the function of the third immunosubunit LMP10/multicatalytic endopeptidase complex-like (MECL)-1 (beta 2i) in MECL-1 gene-targeted mice. The number of CD8(+) splenocytes in MECL-1(-/-) mice was 20% lower than in wild-type mice. Infection with lymphocytic choriomeningitis virus (LCMV) elicited a markedly reduced cytotoxic T cell (CTL) response to the LCMV epitopes GP276-286/D-h and NP205-212/K-b in MECL-1(-/-) mice. The weak CTL response to GP276-286/D-b was not due to an impaired generation of this epitope but was attributed to a decreased precursor frequency of GP276-286D(b) -specific T cells. The expansion of TCR-V(beta)10(+) T cells, which contain GP276-286/D-b-specific cells, was reduced in LCMV-infected MECL-1(-/-) mice. Taken together, our data reveal an in vivo function of MECL-1 in codetermining the T cell repertoire for an antiviral CTL response.