title: Beta2-microglobulin gene mutations in human melanoma cells: molecular characterization and implications for immune surveillance.
abstract: In recent years, the mechanisms underlying defects in the expression/function of human leukocyte antigen (HLA) class I antigens have been analyzed in an increasing number of melanoma cells, since these abnormalities are likely to have a negative impact on T-cell-based immunotherapy of melanoma. This article reviews the information about the molecular defects found in melanoma cell lines that do not express HLA class I antigens, following a concise description of the structure and assembly of HLA class I antigens. Distinct defects ranging from large deletions to point mutations in beta2-microglobulin genes have been found in melanoma cells. A mutation in an 8 base-pair CT repeat region of exon 1 has been found frequently in melanoma cell lines suggesting that this region of the beta2-microglobulin gene is a hot-spot for mutations. The effects of beta2-microglobulin mutations are mostly at the level of translation, emphasizing the importance of analyzing beta2-microglobulin expression at the protein level in melanoma lesions without detectable HLA class I antigen expression. Interestingly, many melanoma cell lines have additional defects that directly impact HLA class I antigen expression. Therefore, multiple mechanisms that affect the expression/function of HLA class I antigens appear to be available to melanoma cells to escape from immune recognition.
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hicklin
authors.forename: D V
authors.initials: DV
authors.lastname: Dellaratta
authors.forename: R
authors.initials: R
authors.lastname: Kishore
authors.forename: B
authors.initials: B
authors.lastname: Liang
authors.forename: T
authors.initials: T
authors.lastname: Kageshita
authors.forename: S
authors.initials: S
authors.lastname: Ferrone
mesh_terms: D005091:Exons; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007157:Immunologic Surveillance / Q000502:physiology*; D008545:Melanoma / Q000235:genetics* / Q000276:immunology*; D017354:Point Mutation; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000276:immunology*
chemical_list: D015395:Histocompatibility Antigens Class I; D001613:beta 2-Microglobulin