Resistance to cell-mediated cytotoxicity is correlated with reduction of H-2K gene products in AKR leukemia

Abstract

AKR leukemia cell lines differing in the amount of H-2K and H-2D antigens expressed on the cell surface were used to assess cell-mediated immune responses in syngeneic mice against Gross/AKR murine leukemia virus (MuLV)-induced tumors. Leukemic cells with reduced expression of H-2Kk antigens were inactive as inducers of Gross-MuLV/H-2k-specific cytotoxic T lymphocytes (CTL) and resistant to lysis by CTL raised against H-2Kk positive AKR leukemia cells. H-2Kk positive leukemias induced cytotoxic effectors, which upon restimulation in vitro, lysed the stimulating and other H-2Kk positive leukemia cells. In antibody inhibition experiments, T-cell-mediated cytotoxicity to these leukemias could only be inhibited by antisera and monoclonal antibodies specific for the H-2Kk antigens. Due to this specific role of H-2Kk antigens in T-cell cytotoxicity to Gross/AKR MuLV-induced tumors, reduced expression of H-2Kk antigens on spontaneous AKR leukemic cells could have important implications for surveillance of these neoplastic cells.

A transcription factor interacting with the class I gene enhancer is inactive in tumorigenic cell lines which suppress major histocompatibility complex class I genes.

“…Thymoma cell lines derived from tumors in ageing AKR mice have different abilities to form leukemias when reintroduced back into animals (14,47,49). Detailed analysis showed that tumorigenicity correlates with expression of MHC class I genes in the cell membrane (47).…”

“…Tumor cells frequently show quantitative alterations in their expression of H-2 molecules compared with cells from the corresponding normal tissues (11,16,46,52,57). Reduced expression of one or more H-2 antigens appears to be associated with the ability of tumor cells to escape surveillance by cytotoxic T lymphocytes and in some cases can facilitate metastatic spread (8,47,58).…”

“…Independently isolated AKR tumor cell lines express variable amounts of H-2Kk molecules on their surface (48). AKR tumor cells with normal or high levels of H-2Kk molecules are readily lysed by cytotoxic T lymphocytes and cannot form tumors when reintroduced into normal AKR mice (14,47). Cell lines with reduced H-2Kk expression cannot be killed by specifically sensitized T lymphocytes and can form tumors.…”

Developmental and tissue-specific expression of the Q5 k gene

“…Because of multiple retroviral insertions adult AKR mice often develop tumors, particularly thymomas. Tumor cells frequently show quantitative or qualitative alterations in their expression of class I molecules which is discussed to be a selective advantage for tumor progression (Jones and Bodmer 1980;Festenstein and Schmidt 1981;Schmidt and Festenstein 1982;Lampson et al 1983;Doyle et al 1985;Schmidt et al 1986). In particular, AKR derived leukemic T-cell lines have been shown to express new H-2 class I specificities (Labeta et al 1989).…”

Interferon‐γ‐Induced MHC Class I Expression and Defects in Jak/Stat Signalling in Methylcholanthrene‐Induced Sarcomas

“…Major histocompatibility complex (MHC) class I molecules are known to play an important role in tumour growth and metastasis [1][2][3][4][5][6][7][8]. Several reports indicate that the level of MHC class I expression on the surface of tumour cells has a decisive influence on whether a tumour will be rejected or accepted when transplanted to histocompatible immunocompetent recipients [9][10][11].…”