Novel human MHC class I genes are expressed by tumour cell lines representing embryonic and extraembryonic tissues.

Abstract

The expression of HLA class I(-like) genes was studied in two human developmental tumour cell lines representing embryonic (Tera-2) and extraembryonic (Jeg-3) origins. Neither cell line expresses polymorphic HLA-A, -B, -C antigens as determined by standard serological typing. Tera-2 cells express the HLA class I-like T cell system A (TCA) determinants; Jeg-3 cells are TCA negative. Northern blot analysis using an HLA class I alpha 3 domain specific probe revealed markedly reduced levels of HLA class I(-like) transcripts in both cell lines, which can be upregulated in Tera-2 cells by incubation with gamma interferon (gamma IFN). Immunoprecipitation studies with a large panel of HLA class I/beta-2 microglobulin (beta 2m) monoclonal antibodies (mAbs), detect low quantities of regular HLA class I heavy chains that are not associated with beta 2m on the surface of Tera-2 cells. In contrast, Jeg-3 cells express significant amounts of cell membrane beta 2m associated molecules of 41 and 45 kilodalton (kD). Screening of a Tera-2 cDNA library, yielded 30 clones that hybridize to a full length HLA class I cDNA probe. Sixteen have been characterized and represent HLA class I sequences, consistent with the haplotype of Tera-2. A similar screening of a Jeg-3 cDNA library isolated clones representing a single novel HLA-C-like sequence; this probably codes for the 45 kD cell surface molecules of Jeg-3. The 41 kD molecule may be encoded by the HLA-6.0 gene since this is constitutively expressed in Jeg-3 cells.