Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes
Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes
复制标题
DOI：
10.1002/eji.200839175
复制
发表时间：
2009-04-01
影响因子：
5.4
通讯作者：
Carrier, Alice
中科院分区：
文献类型：
--
作者：
Gommeaux, Julien;Gregoire, Claude;Carrier, Alice
胸腺特异性丝氨酸蛋白酶（TSSP）最初被报道为在皮质胸腺上皮细胞（cTEC）的内体区室中特异性表达的推定蛋白酶。因此，TSSP潜在地参与自身肽的呈递，所述自身肽与在cTEC表面表达的MHC If类分子结合，并且参与CD 4（+）胸腺细胞的阳性选择。我们通过产生缺失Prss 16（编码TSSP的基因）的突变小鼠来验证这一假设。TSSP缺陷型小鼠产生正常数量的T细胞，尽管表达高表面水平MHC II类的cTEC的百分比降低。通过使用表达MHC II类限制性TCR转基因（Marilyn和OT-II）的敏感转基因模型，我们发现TSSP的缺失显著损害了Marilyn和OT-II CD 4（+）T细胞的选择。相反，表达MHC I类限制性TCR转基因（OT-I）的CD 8（+）T细胞的选择不受影响。因此，TSSP参与某些CD 4（+）T淋巴细胞的阳性选择，并可能构成第一个丝氨酸蛋白酶，在胸腺内呈递与MHC II类复合物结合的自身肽中发挥功能。
Thymus-specific serine protease (TSSP) was initially reported as a putative protease specifically expressed in the endosomal compartment of cortical thymic epithelial cells (cTEC). As such, TSSP is potentially involved in the presentation of the self-peptides that are bound to MHC class If molecules expressed at the cTEC surface and are involved in the positive selection of CD4(+) thymocytes. We tested this hypothesis by generating mutant mice deprived of Prss16, the gene encoding TSSP. TSSP-deficient mice produced normal numbers of T cells, despite a decrease in the percentage of cTEC expressing high surface levels of MHC class II. By using sensitive transgenic models expressing MHC class II-restricted TCR transgenes (Marilyn and OT-II), we showed that the absence of TSSP markedly impaired the selection of Marilyn and OT-II CD4(+) T cells. In contrast, selection of CD8(+) T cells expressing an MHC class I-restricted TCR transgene (OT-I) was unaffected. Therefore, TSSP is involved in the positive selection of some CD4(+) T lymphocytes and likely constitutes the first serine protease to play a function in the intrathymic presentation of self-peptides bound to MHC class II complexes.