Immunogenicity of constitutively active V599EBRaf
Immunogenicity of constitutively active V599EBRaf
复制标题
DOI：
10.1158/0008-5472.can-04-0937
复制
发表时间：
2004-08-01
期刊：
影响因子：
11.2
通讯作者：
Becker, JC
中科院分区：
文献类型：
--
作者：
Andersen, MH;Fensterle, J;Becker, JC
激活型BRAF激活型体细胞错义突变存在于60-66%的黑色素瘤中。其中绝大多数是用谷氨酸取代缬氨酸(V599E)。在这里，我们展示了针对来自(V599E)BRAF的表位的自发的HLA-B*2705重排的细胞毒性T细胞反应。这些T细胞反应是突变特异性的，因为来自野生型BRAF的相应表位不被识别。在具有(V599E)BRAF特异性T细胞反应的患者中，(V599E)BRAF基因在从原发黑色素瘤进展到转移性黑色素瘤的过程中丢失，表明荷瘤宿主对非突变黑色素瘤克隆的主动免疫选择。
Activating BRAF somatic missense mutations within the kinase domain are present in 60-66% of melanomas. The vast majority of these represent a single substitution of glutamate for valine (V599E). Here, we demonstrate spontaneous HLA-B*2705-restrieted cytotoxic T-cell responses against an epitope derived from (V599E)BRaf. These T-cell responses were mutation specific as the corresponding epitope derived from wildtype BRaf was not recognized. The loss of the (V599E)BRAF genotype during progression from primary to metastatic melanoma in patients with (V599E)BRaf specific T-cell responses suggests an active immune selection of nonmutated melanoma clones by the tumor-bearing host.