Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression
- PMID: 1898655
- PMCID: PMC295046
- DOI: 10.1172/JCI114984
Lack of HLA class I antigen expression by cultured melanoma cells FO-1 due to a defect in B2m gene expression
Abstract
The melanoma cell line FO-1 does not express HLA class I antigens and does not acquire them on the cell surface after incubation with IFN-gamma. Immunochemical studies showed that FO-1 cells synthesize HLA class I heavy chain, but do not synthesize beta 2-microglobulin (beta 2-mu). The latter abnormality is associated with lack of beta 2-mu mRNA which remains undetectable in FO-1 cells incubated with IFN-gamma. The defect was identified as a genetic lesion in the B2m gene, since DNA hybridization analysis detected a deletion of the first exon of the 5'-flanking region, and of a segment of the first intron of the B2m gene. HLA class I antigen expression was reconstituted on melanoma cells FO-1 after transfection with the wild-type mouse B2m gene, thereby confirming the abnormality of the endogenous B2m gene. The defect identified in FO-1 cells is distinct from that underlying the lack of HLA class I antigen expression by lymphoblastoid cells Daudi, but is remarkably similar to that causing lack of H-2 class I antigen expression by mouse lymphoblastoid cells R1 (TL-). These results suggest that genetic recombination in the 5' region of the B2m gene is a recurrent mechanism in B2m gene defects. In addition to contributing to our understanding of molecular abnormalities in HLA class I antigen expression by melanoma cells, FO-1 cells represent a useful model for analyzing the role of HLA class I antigens in the biology of melanoma cells and in their interaction with cells of the immune system.
Similar articles
-
Reduction in susceptibility to natural killer cell-mediated lysis of human FO-1 melanoma cells after induction of HLA class I antigen expression by transfection with B2m gene.J Clin Invest. 1991 Jul;88(1):282-9. doi: 10.1172/JCI115289. J Clin Invest. 1991. PMID: 1905328 Free PMC article.
-
Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA.J Clin Invest. 1993 Feb;91(2):684-92. doi: 10.1172/JCI116249. J Clin Invest. 1993. PMID: 8432869 Free PMC article.
-
Induction and functional characterization of beta2-microglobulin (beta2-mu)-free HLA class I heavy chains expressed by beta2-mu-deficient human FO-1 melanoma cells.Eur J Immunol. 1998 Sep;28(9):2817-26. doi: 10.1002/(SICI)1521-4141(199809)28:09<2817::AID-IMMU2817>3.0.CO;2-M. Eur J Immunol. 1998. PMID: 9754569
-
Beta2-microglobulin gene mutations in human melanoma cells: molecular characterization and implications for immune surveillance.Melanoma Res. 1997 Aug;7 Suppl 2:S67-74. Melanoma Res. 1997. PMID: 9578419 Review.
-
Effects of alpha-interferon on serum beta-2-microglobulin.Leuk Lymphoma. 1996 Apr;21(3-4):233-8. doi: 10.3109/10428199209067605. Leuk Lymphoma. 1996. PMID: 8726404 Review.
Cited by
-
Understanding and overcoming resistance to immunotherapy in genitourinary cancers.Cancer Biol Ther. 2024 Dec 31;25(1):2342599. doi: 10.1080/15384047.2024.2342599. Epub 2024 Apr 17. Cancer Biol Ther. 2024. PMID: 38629578 Free PMC article. Review.
-
Diverse cytomegalovirus US11 antagonism and MHC-A evasion strategies reveal a tit-for-tat coevolutionary arms race in hominids.Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2315985121. doi: 10.1073/pnas.2315985121. Epub 2024 Feb 20. Proc Natl Acad Sci U S A. 2024. PMID: 38377192 Free PMC article.
-
Antitumor Immune Responses in B2M-Deficient Cancers.Cancer Immunol Res. 2023 Dec 1;11(12):1642-1655. doi: 10.1158/2326-6066.CIR-23-0139. Cancer Immunol Res. 2023. PMID: 37801341 Free PMC article.
-
Engineering Cell Lines for Specific Human Leukocyte Antigen Presentation.Methods Mol Biol. 2023;2691:351-369. doi: 10.1007/978-1-0716-3331-1_25. Methods Mol Biol. 2023. PMID: 37355557
-
Addressing resistance to PD-1/PD-(L)1 pathway inhibition: considerations for combinatorial clinical trial designs.J Immunother Cancer. 2023 May;11(5):e006555. doi: 10.1136/jitc-2022-006555. J Immunother Cancer. 2023. PMID: 37137552 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous