Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line

Michael K. Jakobsen, Nicholas P. Restifo, Peter A. Cohen, Francesco M. Marincola, L. Bryan Cheshire, W. Marston Linehan, Steven A. Rosenberg, Richard B. Alexander

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We studied major histocompatibility complex (MHC) class I expression in 12 tumor cell culture lines established from patients with metastatic renal cell carcinoma (RCC). In one of these cell culture lines, UOK 123, we found no surface expression of β2-microglobulin (β2m) and MHC class I by flow cytometry. Immunofluorescence staining using three different monoclonal antibodies to p2m revealed no detectable β2β2endoplasmic reticulum (ER), Golgi apparatus, cytoplasm, or on the cell surface. There was no evidence of folded class I molecules inside or on the surface of the cells; however, the ER stained intensively for unfolded class I molecules. Transient expression of (32m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for β2m resulted in normal expression of both β2m and class I (HLA-A, B, C) determinants assessed by flow cytometry analysis. No expression of class I or β2m was seen with the recombinant vaccinia vector carrying a control gene. The inability of class I molecules to reach the cell surface is due to the requirement of β2m for proper folding and presentation of the class I MHC complex. The failure to assemble and express MHC class I complex on the cell surface renders these cells incapable of antigen presentation to cytotoxic T cells and provides a mechanism for escape from immune recognition by the tumor.

Original languageEnglish (US)
Pages (from-to)222-228
Number of pages7
JournalJournal of Immunotherapy
Volume17
Issue number4
DOIs
StatePublished - May 1995

Keywords

  • MHC class I
  • Renal cell carcinoma
  • β-microglobulin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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