Suppression of class I human histocompatibility leukocyte antigen by c- myc is locus specific

doi:10.1084/jem.170.3.621

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Suppression of class I human histocompatibility leukocyte antigen by c- myc is locus specific

R Versteeg, KM Kruse-Wolters, AC Plomp, A van Leeuwen, NJ Stam, HL Ploegh, DJ Ruiter and PI Schrier
Department of Clinical Oncology, University Hospital Leiden, The Netherlands.

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.
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