Defective major histocompatibility complex class I expression in a sarcomatoid renal cell carcinoma cell line.
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 beta 2-microglobulin (beta 2m) and MHC class I by flow cytometry. Immunofluorescence staining using three different monoclonal antibodies to beta 2m revealed no detectable beta 2m in the endoplasmic 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 beta 2m by UOK 123 after infection with a recombinant vaccinia virus containing the gene for beta 2m resulted in normal expression of both beta 2m and class I (HLA-A, B, C) determinants assessed by flow cytometry analysis. No expression of class I or beta 2m 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 beta 2m 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.
Jakobsen
M K
MK
Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA.
Restifo
N P
NP
Cohen
P A
PA
Marincola
F M
FM
Cheshire
L B
LB
Linehan
W M
WM
Rosenberg
S A
SA
Alexander
R B
RB
D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D002296:Carcinosarcoma / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D005434:Flow Cytometry; D005805:Genes, MHC Class I / Q000276:immunology*; D005802:Genes, MHC Class II / Q000276:immunology; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007424:Intracellular Fluid / Q000737:chemistry; D018613:Microscopy, Confocal; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics; D001613:beta 2-Microglobulin / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin