The induction of class I HLA by interferon-alpha is independent of the cell cycle, but the expression is enhanced by a G1/S block.

Abstract

The induction of class I HLA expression by interferon-alpha (IFN-alpha) was studied in lymphoid cells arrested or traversing different stages of the cell cycle. Exponential cultures of MOLT-4 cells and the MOLT-4 cell variant YHHH were treated with the cell cycle inhibitors aphidicolin and colcemid to obtain cell populations arrested in G1/S and G2/M, respectively, and also cells traversing from S to M and vice versa. Cytofluorimetry with the monoclonal antibody YTH/76.3 (which specifically detects those class I molecules which are most susceptible to IFN-alpha induction) was used to quantitate the class I HLA response to IFN-alpha. The results showed that the response to IFN-alpha is not restricted to a given stage of the cell cycle. These studies also revealed that when the cells were arrested at G1/S, the absolute level of class I HLA expression was enhanced 2-3-fold, both in the presence or absence of either IFN-alpha or IFN-gamma. Therefore, even when absolute levels changed, the ratio of IFN-induced expression to basal expression remained constant at all cell cycle stages. The level of expression of another surface antigen (the CD1 antigen HTA-1) was not affected by the G1/S block. The results were confirmed by dot blot hybridization of poly(A)+ RNA using cDNA-specific probes. These findings suggest that the effect of IFN-alpha is continuous throughout the cell cycle but that a G1-dependent event determines the extent of class I HLA expression, and leads to a synergistic superinduction by IFN in G1/S-arrested cells.