Cutting edge: permissive MHC class II allele changes the pattern of antitumor immune response resulting in failure of tumor rejection.
Cutting edge: permissive MHC class II allele changes the pattern of antitumor immune response resulting in failure of tumor rejection.
复制标题
DOI：
10.4049/jimmunol.182.3.1242
复制
发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Alexander RB
中科院分区：
文献类型：
--
作者：
Klyushnenkova EN;Kouiavskaia DV;Berard CA;Alexander RB
我们研究了表达人类前列腺特异性抗原 (PSA) 的转基因小鼠前列腺腺癌 (TRAMP)-C1 肿瘤细胞在 HLA-DRB1*1501 (DR2b) 转基因小鼠中的生长。 TRAMP-PSA 肿瘤经常被 HLA-DR2b- 小鼠排斥，但在 HLA-DR2b+ 同窝小鼠中发生率增加。与携带 HLA-DR2b+ 肿瘤的同窝小鼠相比，排斥 TRAMP-PSA 肿瘤的 HLA-DR2b- 小鼠中 PSA 特异性 CD8 T 细胞反应水平显着更高。相反，在携带 TRAMP-PSA 肿瘤的 HLA-DR2b+ 小鼠中，对 PSA 的抗体反应很强，而在 HLA-DR2b- 同窝小鼠中几乎检测不到。 CD4 T 细胞对 PSA 反应的分析揭示了 HLA-DR2b+ 小鼠中存在多个 CD4 T 细胞表位，但未能在 HLA-DR2b- 小鼠中鉴定出强 I-Ab 限制性表位。我们的数据表明，允许的 HLA II 类等位基因的表达可以改变对肿瘤抗原的免疫反应模式，导致肿瘤排斥失败。
We studied the growth of transgenic adenocarcinoma of mouse prostate (TRAMP)-C1 tumor cells expressing human prostate specific antigen (PSA) in HLA-DRB1*1501 (DR2b) transgenic mice. TRAMP-PSA tumors were frequently rejected by HLA-DR2b- mice but had increased incidence in HLA-DR2b+ littermates. The levels of PSA-specific CD8 T cell responses were significantly higher in HLA-DR2b- mice that rejected TRAMP-PSA tumors compared to HLA-DR2b+ tumor-bearing littermates. In contrast, antibody responses to PSA were strong in HLA-DR2b+ mice bearing TRAMP-PSA tumors and were virtually undetectable in HLA-DR2b- littermates. The analysis of CD4 T cell responses to PSA revealed the presence of several CD4 T cell epitopes in HLA-DR2b+ mice, but failed to identify strong I-Ab-restricted epitopes in HLA-DR2b- mice. Our data demonstrate that the expression of a permissive HLA class II allele can change the pattern of the immune response to a tumor antigen resulting in the failure of tumor rejection.
登录
查看更多内容
影响因子：
6.6
作者：
McNeel, DG;Nguyen, LD;Disis, ML
通讯作者：
Disis, ML
影响因子：
30.8
作者：
Madsen, LS;Andersson, EC;Fugger, L
通讯作者：
Fugger, L
影响因子：
3.9
作者：
Klyushnenkova, EN;Ponniah, S;Alexander, RB
通讯作者：
Alexander, RB
影响因子：
2.8
作者：
Pavlenko, M;Leder, C;Pisa, P
通讯作者：
Pisa, P
影响因子：
11.5
作者：
Klyushnenkova, EN;Link, J;Alexander, RB
通讯作者：
Alexander, RB