MHC class II-mediated antigen presentation by melanoma cells
MHC class II-mediated antigen presentation by melanoma cells
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DOI：
10.1097/00002371-199611000-00001
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发表时间：
1996-11-01
影响因子：
3.9
通讯作者：
Lee, JS
中科院分区：
文献类型：
--
作者：
Brady, MS;Eckels, DD;Lee, JS
主要组织相容性复合体（MHC）II类分子的组成型表达通常限于免疫系统的专职抗原呈递细胞（APC），尽管它也经常发生在黑素瘤中。提示黑色素瘤的MHC LI类表达与肿瘤进展相关的临床证据使我们假设MHC II类介导的抗原呈递在这种疾病中的作用。首先，我们研究了来自转移瘤的黑色素瘤细胞是否可以加工抗原和/或将肽vi MHC II类分子呈递给肽特异性CD 4（+）T细胞克隆。在测试的所有细胞系中，黑色素瘤细胞能够加工抗原并有效地将肽呈递给CD 4（+）T细胞，导致T细胞增殖比对照增加5-26倍。接下来，我们发现不需要CD 28介导的共刺激，因为用CTLA-4 Ig阻断对T细胞对黑色素瘤或B细胞作为APC的应答没有影响。相反，阻断CD 54（ICAM-1）导致黑色素瘤细胞对肽呈递的增殖反应降低，而B细胞则没有。这些数据表明，黑色素瘤细胞上的MHC II类分子是功能性的，抗原加工途径是完整的。此外，CD 54似乎在黑色素瘤的肽呈递中发挥重要作用。
Constitutive expression of major histocompatibility complex (MHC) class II molecules is normally restricted to professional antigen-presenting cells (APCs) of the immune system, although it also occurs frequently in melanoma. Clinical evidence suggesting that MHC class LI expression by melanoma is associated with tumor progression led us to postulate a role for MHC class II mediated antigen presentation in this disease. First, we investigated whether melanoma cells derived from metastases can process antigen and/or present peptide vi MHC class II molecules to a peptide-specific CD4(+) T-cell clone. In all cell lines tested, melanoma cells were able to process antigen and present peptide efficiently to CD4(+) T cells, resulting in T-cell proliferation increased 5-26-fold over controls. Next, we found that CD28-mediated costimulation was not required, because blocking with CTLA-4Ig had no effect on the T-cell response to either melanoma or B cells as APCs. In contrast, blocking CD54 (ICAM-1) resulted in a decrease in proliferation in response to peptide presentation by melanoma but not B cells. These data demonstrate that MHC class II molecules on melanoma cells are functional and that antigen-processing pathways are intact. In addition, CD54 seems to play a significant role in peptide presentation by melanoma.