Suppression of class I human histocompatibility leukocyte antigen by c-myc is locus specific.
The c-myc oncogene downregulates class I HLA expression in human melanoma. The major class I HLA antigens are encoded by three loci, A, B, and C, and we investigated whether these loci are suppressed equally by c-myc. In three melanoma cell lines with high c-myc expression, we analyzed mRNA, protein, and cell surface expression of the class I HLA antigens. Whereas the HLA-B locus expression was found to be strongly reduced, the HLA-A locus was expressed normally. Analysis of c-myc-transfected clones of two melanoma cell lines confirmed that c-myc preferentially suppresses the class I HLA-B locus. Immunohistochemical analysis of fresh melanoma lesions also showed that in the tumors the HLA-A loci are expressed normally, while on the majority of tumor cells no HLA-B antigen expression was found. This downregulation may have consequences for the recognition of malignant cells by tumor-infiltrating lymphocytes. Our results predict that HLA-B-restricted cytotoxic T cells will be unable to kill high c-myc-expressing melanoma cells.
Versteeg
R
R
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.
Krüse-Wolters
K M
KM
Plomp
A C
AC
van Leeuwen
A
A
Stam
N J
NJ
Ploegh
H L
HL
Ruiter
D J
DJ
Schrier
P I
PI
D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000276:immunology; D051379:Mice; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger