αvβ3-dependent cross-presentation of matrix metalloproteinase-2 by melanoma cells gives rise to a new tumor antigen
αvβ3-dependent cross-presentation of matrix metalloproteinase-2 by melanoma cells gives rise to a new tumor antigen
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DOI：
10.1084/jem.20042138
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发表时间：
2005-07-04
影响因子：
15.3
通讯作者：
Guilloux, Y
中科院分区：
文献类型：
--
作者：
Godefroy, E;Moreau-Aubry, A;Guilloux, Y
已经鉴定了由肿瘤特异性T细胞识别的大量抗原，并显示其通过各种过程产生。我们描述了一种新的机制，T细胞识别黑色素瘤细胞，这涉及产生的主要组织相容性复合物I类限制性表位后，肿瘤介导的摄取和加工的细胞外蛋白质-一个过程称为交叉呈递-这被认为是限制于免疫细胞。我们发现，黑色素瘤细胞交叉目前，在α v β 3依赖的方式，来自分泌的基质金属蛋白酶-2（MMP-2）的抗原，人类白细胞抗原A*0201限制性T细胞。因为MMP-2活性对于黑素瘤进展是关键的，所以MMP-2肽应该由大多数进展的黑素瘤交叉呈递，并且代表用于这些肿瘤的疫苗治疗的独特抗原。
A large array of antigens that are recognized by tumor-specific T cells has been identified and shown to be generated through various processes. We describe a new mechanism underlying T cell recognition of melanoma cells, which involves the generation of a major histocompatibility complex class I-restricted epitope after tumor-mediated uptake and processing of an extracellular protein - a process referred to as cross-presentation - which is believed to be restricted to immune cells. We show that melanoma cells cross-present, in an alpha v beta 3-dependent manner, an antigen derived from secreted matrix metalloproteinase - 2 (MMP-2) to human leukocyte antigen A*0201-restricted T cells. Because MMP-2 activity is critical for melanoma progression, the MMP-2 peptide should be cross-presented by most progressing melanomas and represents a unique antigen for vaccine therapy of these tumors.