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Analysis of the MHC Class I Antigen Presentation Machinery in Human Embryonal Carcinomas: Evidence for Deficiencies in TAP, LMP and MHC Class I Expression and their Upregulation by IFN‐γ
Author(s) -
SELIGER B.,
DUNN T.,
SCHWENZER A.,
CASPER J.,
HUBER C.,
SCHMOLL H. J.
Publication year - 1997
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1997.d01-176.x
Subject(s) - transporter associated with antigen processing , antigen processing , mhc class i , biology , major histocompatibility complex , antigen presentation , antigen , downregulation and upregulation , human leukocyte antigen , cd74 , cd8 , mhc class ii , microbiology and biotechnology , mhc restriction , interferon gamma , immunology , immune system , t cell , gene , genetics
The expression of the major histocompatibility complex (MHC) class I antigens is suppressed in early post‐implantation embryonic cells as well as in embryonal carcinoma (EC) cells, but could be upregulated by treatment with interferon (IFN)‐γ or retinoic acid. In a number of human and murine tumours, defects in the expression of the different components of the MHC class I antigen processing machinery, such as the proteasomal subunits LMP‐2 and LMP‐7 and the peptide transporters TAP‐1 and TAP‐2, account for impaired MHC class I surface expression. Here, we analysed the constitutive and IFN‐γ regulated mRNA and protein expression of the LMP, TAP and MHC class I molecules in the human EC line 577LM. In comparison to lymphoblastoid control cells, poor constitutive mRNA and protein expression of LMP‐7, TAP‐1, HLA class I, and β 2 ‐microglobulin, but not of TAP‐2 and LMP‐2, was detected in 577LM cells. The lack of MHC class I surface expression on 577LM cells could not be enhanced either by culturing cells at low temperature or by their incubation with exogenous MHC class I specific binding peptides: thus, the defective MHC class I surface expression was not only caused by impaired generation and processing of antigenic peptides. IFN‐γ treatment of 577LM resulted in a significant increase of MHC class I surface expression which was preceded by an upregulation of TAP, LMP and MHC class I transcripts as well as of TAP‐1 and TAP‐2, but not of LMP‐2 and LMP‐7, protein expression. These data suggest that human EC cell lines show a stable expression of a MHC class I low/deficient phenotype. The deficiencies associated with this phenotype involve different levels of the MHC class I restricted antigen presentation machinery and could be modified by treatment with IFN‐γ.