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 journalArticle

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
StatePublished - 1995
Externally publishedYes

Fingerprint

Major Histocompatibility Complex
Renal Cell Carcinoma
Cell Line
Flow Cytometry
Cell Culture Techniques
Tumor Escape
Vaccinia
Reticulum
HLA-A Antigens
HLA-B Antigens
Vaccinia virus
Antigen Presentation
Golgi Apparatus
Tumor Cell Line
Genes
Fluorescent Antibody Technique
Cytoplasm
Monoclonal Antibodies
Staining and Labeling
T-Lymphocytes

Keywords

  • MHC class I
  • Renal cell carcinoma
  • β<inf>2</inf>-microglobulin

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Immunology and Allergy
  • Pharmacology

Cite this

Jakobsen, M. K., Restifo, N. P., Cohen, P. A., Marincola, F. M., Bryan Cheshire, L., Marston Linehan, W., ... Alexander, R. B. (1995). Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line. Journal of Immunotherapy, 17(4), 222-228.

Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line. / Jakobsen, Michael K.; Restifo, Nicholas P.; Cohen, Peter A.; Marincola, Francesco M.; Bryan Cheshire, L.; Marston Linehan, W.; Rosenberg, Steven A.; Alexander, Richard B.

In: Journal of Immunotherapy, Vol. 17, No. 4, 1995, p. 222-228.

Research output: Contribution to journalArticle

Jakobsen, MK, Restifo, NP, Cohen, PA, Marincola, FM, Bryan Cheshire, L, Marston Linehan, W, Rosenberg, SA & Alexander, RB 1995, 'Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line', Journal of Immunotherapy, vol. 17, no. 4, pp. 222-228.
Jakobsen MK, Restifo NP, Cohen PA, Marincola FM, Bryan Cheshire L, Marston Linehan W et al. Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line. Journal of Immunotherapy. 1995;17(4):222-228.
Jakobsen, Michael K. ; Restifo, Nicholas P. ; Cohen, Peter A. ; Marincola, Francesco M. ; Bryan Cheshire, L. ; Marston Linehan, W. ; Rosenberg, Steven A. ; Alexander, Richard B. / Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line. In: Journal of Immunotherapy. 1995 ; Vol. 17, No. 4. pp. 222-228.
@article{b58d24c91c0b481d8ed5eff9f5e4e2b1,
title = "Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line",
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.",
keywords = "MHC class I, Renal cell carcinoma, β<inf>2</inf>-microglobulin",
author = "Jakobsen, {Michael K.} and Restifo, {Nicholas P.} and Cohen, {Peter A.} and Marincola, {Francesco M.} and {Bryan Cheshire}, L. and {Marston Linehan}, W. and Rosenberg, {Steven A.} and Alexander, {Richard B.}",
year = "1995",
language = "English (US)",
volume = "17",
pages = "222--228",
journal = "Journal of Immunotherapy",
issn = "1524-9557",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Defective major histocompatibility complex class i expression in a sarcomatoid renal cell carcinoma cell line

AU - Jakobsen, Michael K.

AU - Restifo, Nicholas P.

AU - Cohen, Peter A.

AU - Marincola, Francesco M.

AU - Bryan Cheshire, L.

AU - Marston Linehan, W.

AU - Rosenberg, Steven A.

AU - Alexander, Richard B.

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - MHC class I

KW - Renal cell carcinoma

KW - β<inf>2</inf>-microglobulin

UR - http://www.scopus.com/inward/record.url?scp=0029123613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029123613&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 222

EP - 228

JO - Journal of Immunotherapy

JF - Journal of Immunotherapy

SN - 1524-9557

IS - 4

ER -