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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen.
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Epitope clustering in regions undergoing efficient proteasomal processing defines immunodominant CTL regions of a tumor antigen.

机译：在经历有效的蛋白酶体加工的区域中的表位簇集定义了肿瘤抗原的免疫显性CTL区域。

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Identification of immunodominant CD8(+) T cell responses to frequently expressed tumor antigens across MHC class I polymorphism is essential for the implementation of cancer immunotherapy. However, the key factors that determine immunodominance are not fully understood. Because of its frequent expression in tumors and its spontaneous immunogenicity, NY-ESO-1 is a prime target of cancer vaccines and an ideal model antigen for elucidating the molecular basis of immunodominant tumor-specific CD8(+) T cell responses. Here, we have assessed CD8(+)T cell responses to full-length NY-ESO-1 in cancer patients. We identified 3 immunodominant regions of the protein located within 3 distinct clusters of MHC class I binding sequences that co-localize with previously defined clusters of MHC class II binding sequences, are predicted to be hydrophobic and undergo efficient proteasomal processing. Our results support the concept that epitope clustering within defined protein regions identifies tumor antigen immunodominant regions and suggest a general strategy for their identification.
机译：跨MHC I类多态性对频繁表达的肿瘤抗原的免疫显性CD8（+）T细胞应答的鉴定对于癌症免疫疗法的实施至关重要。但是，尚未完全了解确定免疫优势的关键因素。由于其在肿瘤中的频繁表达及其自发的免疫原性，NY-ESO-1是癌症疫苗的主要靶标，也是阐明免疫显性肿瘤特异性CD8（+）T细胞反应的分子基础的理想模型抗原。在这里，我们评估了癌症患者对全长NY-ESO-1的CD8（+）T细胞反应。我们确定了位于3个MHC I类结合序列的不同簇中的蛋白质的3个免疫优势区域，这些簇与先前定义的MHC II类结合序列的簇共定位，被预测为疏水性的，并经历了有效的蛋白酶体加工。我们的结果支持这样的概念，即在定义的蛋白质区域内的抗原决定簇簇可识别肿瘤抗原的免疫优势区域，并提出了对其进行鉴定的一般策略。

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