Reduced Recognition of Metastatic Melanoma Cells by Autologous MART-1 Specific CTL: Relationship to TAP Expression
作者:
James Murray,
J. Hudson,
Merrick Ross,
Hua-Zhong Zhang,
Constantin Ioannides,
期刊:
Journal of Immunotherapy
(OVID Available online 2000)
卷期:
Volume 23,
issue 1
页码: 28-35
ISSN:1524-9557
年代: 2000
出版商: OVID
关键词: Melanoma;HLA class I;TAP;Immunosurveillance
数据来源: OVID
摘要:
Class I expression in context with T-cell receptor expression is crucial for peptide presentation and induction of CD8+ cytotoxic T lymphocytes (CTL). Presentation of class I bound peptides is dependent on transporter-associated proteins (TAP) expression and function. Tumor infiltrating lymphocytes from a patient with melanoma were isolated, expanded in vitro in the presence of interleukin-2, and tested for cytotoxicity against HLA-A2 positive, MART-1 positive autologous tumor cells, an HLA-A2-positive, MART-1 positive melanoma cell line (Mel-501), and HLA-A2-negative melanoma cells. Significant killing occurred against both A2-positive cell lines (63% and 65%, respectively), but not against the A2-negative line (18%) or A2-positive autologous tumor (1.5%). These CTL preferentially recognized the MART-1 peptide F119, 27–35, and gp100 peptide F125, 280–288, resulting in a 30% to 60% enhancement of lysis when autologous tumor or major histocompatibility complex class I “empty” T2 cells were pulsed with either peptide. To address whether the deficiency in autologous tumor recognition might be related to a deficiency in Ag presentation, we screened for the presence of TAP1 and TAP2 transcripts by polymerase chain reaction, Southern blotting, and scanning densitometry using sequence-specific primers and probes. Both TAP1 and TAP2 expression levels in the autologous tumor were minimal, yet were upregulated 7-to 18-fold, respectively, by interferon-&ggr;. Despite this increase, a similar increase in cytotoxicity did not occur. In short, deficiencies in TAP presentation may have functional significance for tumor escape from immunosurveillance and with respect to impending vaccine trials.
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