HLA-B down-regulation in human melanoma is mediated by sequences located downstream of the transcription-initiation site

Major histocompatibility complex (MHC, HLA in humans) class I molecules pla y an important role in cellular immunology by presenting viral, tumor-assoc iated or minor histocompatibility antigen derived peptides to T cells. Tumo r 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 prima ry human melanomas as well as melanoma cell lines, HLA class I expression i s frequently down-regulated in a B locus-specific manner. The HLA class I p romoter contains a number of cis-regulatory elements located upstream of th e transcription-initiation site, among them enhancer A and an interferon-st imulated response element. In the present study, we show that novel sequenc es located 13 to 33 bp downstream of the transcription-initiation site medi ate HLA-B locus-specific down-regulation in human melanoma cell lines. Furt hermore, involvement of the +13 to +33-bp region in HLA-B locus-specific do wn-regulation in vivo is supported by in vitro experiments showing locus-sp ecific binding of protein complexes to the +13 to +33-bp region. (C) 1999 W iley-Liss, Inc.