Down-Regulation of the Transporter for Antigen Presentation, Proteasome Subunits, and Class I Major Histocompatibility Complex in Tumor Cell Lines

作者: Alyssa Johnsen , John France , Man-Sun Sy , Clifford V Harding

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摘要: Abstract Tumor cells may alter the expression of proteins involved in antigen processing and presentation, allowing them to avoid recognition elimination by cytotoxic T cells. In this study, reverse transcription-PCR was used assess human tumor cell lines mRNA for multiple components class I MHC antigen-processing pathway, including several proteasome subunits that have been implicated but not previously examined context (e.g., low molecular weight polypeptide subunit (LMP) 10, activator (PA) 28α, PA28β). Deficiencies genes were demonstrated 9 27 lines, representing a variety histological types. some cases, virtually complete deficiencies observed four encoded within (TAP1, TAP2, LMP2, LMP7), as well LMP10, which is outside MHC. Combined these gene products common, marked deficiency LMP10 found five nine with deficits. The existence at dispersed loci suggested basis regulatory mechanism, opposed mutation or deletion genes. Furthermore, most reversed treatment IFN-γ. contrast such extreme deficiencies, we unaltered only partially decreased PA28α PA28β lines. Thus, tumors evade immune surveillance simultaneously down-regulating MHC-I thereby altering presentation antigens. Expression essential subunits, however, still be maintained.

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