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HLA‐B down‐regulation in human melanoma is mediated by sequences located downstream of the transcription‐initiation site
Author(s) -
Griffioen Marieke,
Ouwerkerk Ilse J.M.,
Harten Veronique,
Schrier Peter I.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990209)80:4<573::aid-ijc15>3.0.co;2-s
Subject(s) - human leukocyte antigen , enhancer , biology , major histocompatibility complex , locus (genetics) , mhc class i , transcription (linguistics) , hla b , genetics , microbiology and biotechnology , transcription factor , antigen , gene , linguistics , philosophy
Major histocompatibility complex (MHC, HLA in humans) class I molecules play an important role in cellular immunology by presenting viral, tumor‐associated or minor histocompatibility antigen‐derived peptides to T cells. Tumor cells frequently fail to express one or more of the different MHC class I loci (HLA‐A, ‐B and ‐C), thereby avoiding elimination by T cells. In primary human melanomas as well as melanoma cell lines, HLA class I expression is frequently down‐regulated in a B locus‐specific manner. The HLA class I promoter contains a number of cis ‐regulatory elements located upstream of the transcription‐initiation site, among them enhancer A and an interferon‐stimulated response element. In the present study, we show that novel sequences located 13 to 33 bp downstream of the transcription‐initiation site mediate HLA‐B locus‐specific down‐regulation in human melanoma cell lines. Furthermore, involvement of the +13 to +33‐bp region in HLA‐B locus‐specific down‐regulation in vivo is supported by in vitro experiments showing locus‐specific binding of protein complexes to the +13 to +33‐bp region. Int. J. Cancer 80:573–580, 1999. © 1999 Wiley‐Liss, Inc.