title: Down-regulation of HLA antigens by the adenovirus type 2 E3/19K protein in a T-lymphoma cell line.
abstract: Adenoviruses of subgroup C can establish persistent infections in human beings. The exact site of persistence has not been established, but lymphoid tissues are certainly one reservoir. Experimental evidence suggests that early transcription unit 3 (E3) of the virus is involved in this phenomenon. In particular, the most abundant protein of this region, the E3/19K protein, seems to fulfill an important role in viral escape from the immune response. We previously demonstrated that in nonlymphoid cells E3/19K interferes with the antigen presentation function of class I major histocompatibility complex (MHC) antigens by inhibiting their transport to the cell surface. However, the function of the E3 products in lymphoid cells was not investigated. To examine this, the T-lymphoma cell line Jurkat was transfected with a DNA fragment comprising the entire E3 region of adenovirus type 2. We show here that E3/19K is expressed in the absence of the viral transactivator E1A with a rate of biosynthesis similar to that in nonlymphoid 293 cells. Furthermore, inhibition of transport and down-regulation of MHC antigens was comparable in both cell lines. In contrast, various T-cell molecules containing immunoglobulin-like domains showed a normal expression pattern in the transfected cells. A detailed analysis of the interaction between E3/19K and the MHC class I antigens of Jurkat (HLA-A3 and HLA-B35) revealed a differential sensitivity for down-regulation by E3/19K. The data demonstrate that E3/19K exerts its function also in lymphoid cells without affecting other lymphoid cell surface molecules. The implications for persistence of adenovirus in lymphoid cells in vivo are discussed.
authors.affiliation: Spermann Laboratories, Max-Planck-Institut für Immunobiologie, Freiburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Körner
authors.forename: H G
authors.initials: HG
authors.lastname: Burgert
mesh_terms: D017503:Adenovirus E3 Proteins / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000254:growth & development*; D001692:Biological Transport; D015536:Down-Regulation; D006031:Glycosylation; D006680:HLA Antigens / Q000096:biosynthesis* / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016399:Lymphoma, T-Cell / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D017503:Adenovirus E3 Proteins; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I