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

The induction of class I HLA expression by interferon‐α (IFN‐α) 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‐α induction) was used to quantitate the class I HLA response to IFN‐α. The results showed that the response to IFN‐α 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‐α or IFN‐γ. 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‐α 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.