表位竞争可削弱针对非优势表位的T细胞应答

Epitope competition weakens specific T cell response to subdominant epitopes

目的阐明表位竞争对特异性T细胞应答强度和功能特征的影响。方法利用pSV—gag92和pSV-env203两个单表位DNA疫苗和pSV-gag／env融合基因疫苗免疫C57BL／6小鼠。免疫结束后，通过细胞内细胞因子染色的方法检测Gag92和Env203特异性T细胞反应，并比较其差异。结果pSV—gag92所活化的Gag92特异性IFN—γ＋CD8T细胞占总CD8T细胞比例[（0．41500±0．04588）％]显著高于pSV—gag／env[（0．05867±0．01964）％]。同时，我们发现pSV—gag／onv所活化的Gag92特异性TNF-α-—IFN-^γ’CD8T细胞平均荧光强度（296．70±14．08）显著低于Env203特异性TNF-（It—IFN-^γ＋CD8T细胞的平均荧光强度（818．00±49．34）。结论表位竞争能够显著降低针对非优势表位的T细胞反应频率和平均强度。

Objective To elucidate the influences of epitope competition on the frequency and av- erage intensity of specific T cell response. Methods C57BL/6 mice were immunized with either single epitope DNA vaccines （pSV-gag92 or pSV-env203 ） or fusion gene DNA vaccine （pSV-gag/env）. Gag92 and Env203 epitope-speeific CD8 T cell responses were analyzed by intracellular cytokine staining assay. Results Gag92-specific IFN-γCD8 T cells that were induced by pSV-gag92 accounted for 0. 415 00% ± 0.045 88% of the total CD8 T cells, which was much more than that induced by pSV-gag/env of 0.058 67%± 0. 019 64%. Moreover, the mean fluorescence intensity of Gag92-specific TNF-α-IFN-γ/CD8 T cells （296.70±14.08） elicited by pSV-gag/env was significantly lower than that of Env203-specific TNF- α-IFN-γ/＋CD8 T cells （818.00±49.34）. Conclusion Epitope competition could significantly decrease both the frequency and the average intensity of specific T cell response to subdominant epitopes.