Partial purification and characterization of a novel human factor that augments the expression of class I MHC antigens on tumour cells.

A cytokine which augments the expression of major histocompatibility complex (MHC) I antigens on K562 and gastric carcinoma tumour (HR) cells, has been isolated from the culture supernatant of Concanavalin-A (Con-A) activated human peripheral blood mononuclear cells. The factor, termed MHC augmenting factor (MHC-AF) has been partially purified by Sephadex G-100 column chromatography, preparative isoelectric focusing and HPLC with ion-exchange as well as sizing columns. MHC-AF activity is associated with a 35 kDa molecule which has pI of 6·0. Interferon (IFN)-α, ß, tumour necrosis factor (TNF), Interleukin (IL)-2, IL-4, IL-5 and IL-7 had no significant effect in MHC-AF bioassay, but IFN-γ had significant MHC-AF activity. Antibodies to IFN-α, IFN-ß and TNF-α did not block the activity of MHC-AF, but anti-IFN-y antibodies could partially neutralize the activity. However, unlike IFN-γ, MHC-AF activity was resistant to pH 2·0 treatment. Purified MHC-AF preparations did not have any activity in WISH cell/encephalo myocarditis virus (EMC) IFN bioassays. In addition, anti-IFN-y affinity column did not retain MHC-AF activity. These results indicate that a MHC-AF distinct from IFN-γ, is produced by activated human mononuclear cells.

Enhanced MHC I antigen expression on tumour target cells is inversely correlated to lysis by allogenic but not by xenogenic NK cells.

Relationship between the levels of MHC class 1 antigen expressed on tumour cells and their susceptibility to allogenic and xenogenic NK cells was investigated. Mouse and human natural killer-resistance inducing factor (NK-RIF) preparations were used for augmenting/inducing MHC 1 antigen expression on murine YAC and human K562 tumour cells, respectively YAC cells with augmented MHC I antigen expression became relatively resistant to lysis by murine NK cells but not to rat NK cells. Similarly, induction of MHC I antigens on K562 cells reduced their susceptibility to human NK cells but not to monkey NK cells. These results indicate that the inverse correlation of MHC I antigen expression and NK susceptibility does not hold true for xenogenic pairs of NK effector and target cells.