title: Reduced membrane major histocompatibility complex class I density and stability in a subset of human renal cell carcinomas with low TAP and LMP expression.
abstract: Suppression of MHC class I expression is thought to allow tumor cells to escape immune surveillance mediated by CD8(+) CTLs. For stable MHC class I surface expression, multiple protein interactions are required for efficient assembly of MHC class I heavy chain and beta 2-microglobulin with endogenous peptides. Peptide processing and transport into the endoplasmic reticulum involves the genes of the transporters associated with antigen processing, TAP-1 and TAP-2, and the two components of the proteasome complex, the low molecular weight proteins LMP-2 and LMP-7. We selected human renal cell carcinoma (RCC) cells derived from a tumor that is thought to be controlled by host immunity to study the MHC class I antigen presentation machinery. Eleven RCC lines established from primary tumors were investigated for the mRNA and protein expression of MHC class I, TAP, and LMP genes. In addition, membrane stability of MHC class I was determined by incubation of the RCC cell lines at low temperature and in the presence of exogenous HLA-binding peptides. Our results revealed the existence of two different phenotypes of RCC cell lines. Group I displayed temperature-stable MHC class I surface expression associated with high, and in most cases coordinated, expression of MHC class I heavy and light chain, TAP and LMP transcripts, and proteins. Group II demonstrated a marked MHC class I instability at 37 degreesC associated with low but coordinated expression of the respective transcripts and proteins. MHC class I membrane expression of group II, but not of group I RCC cells, could be stabilized by incubation with specific MHC class I binding peptides. These results suggest an important role of the genes of the antigen presentation machinery in stable and efficient MHC class I surface expression of RCC cells. However, it has still to be defined whether deficient antigen processing is one of the mechanisms of RCC cells to escape the surveillance of the immune system.
authors.affiliation: The Johannes Gutenberg University, Third Department of Internal Medicine, Division of Hematology/Oncology, Langenbeckstr. 1, 55131 Mainz, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Seliger
authors.forename: A
authors.initials: A
authors.lastname: Höhne
authors.forename: A
authors.initials: A
authors.lastname: Knuth
authors.forename: H
authors.initials: H
authors.lastname: Bernhard
authors.forename: B
authors.initials: B
authors.lastname: Ehring
authors.forename: R
authors.initials: R
authors.lastname: Tampé
authors.forename: C
authors.initials: C
authors.lastname: Huber
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000032:analysis* / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000276:immunology*; D003546:Cysteine Endopeptidases; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D006801:Humans; D007680:Kidney Neoplasms / Q000276:immunology*; D009097:Multienzyme Complexes; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D013696:Temperature; D014407:Tumor Cells, Cultured
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D011506:Proteins; D012333:RNA, Messenger; C073119:TAP1 protein, human; C071313:LMP-2 protein; C071692:TAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex