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The expression of CIITA in vitro in cell lines is controlled by 3 different CllTA promoters in a common open reading frame: P.I for dendrttic cells, P.III for B cells, and P.IV for IFN-y induction (EMB0 J 16.2851, 1997). However, the role of each promoter in the different patterns of class II expression observed in vivo is unknown. We studied expression of CIITA promoters in tissues of mice in the basal and stimulated states of CIITA and class II expression, by an RT-PCR system with promoter specific 5'primers and probes for mRNA 5"ends. We also examined the dependency of each promoter on transcription factor IRF-1, using IRF-1 knockout mice. Basal CIITA expression was highly expressed in spleen. skin, and kidney. P.III was expressed mainly in spleen (with abundant B cells) and was independent of IRF-1, and not increased by allogeneic stimulation or by IFN-y. P.I was expressed in the basal state in many tissues, correlating with dendritic cell content, and was not increased by IFNy, and was IRF-1 independent. P.IV was expressed in the basal state in skin, spleen, and kidney, was increased by allostimulation correlating with parenchymal class II induction in tissue section, and was increased by rlFN-y, and was IRF-1 dependent.
Thus, basal activity of CIITA (and the class II antigen presenting system) reflects the activity of P.I (in dendritic cells) and some IFN-y induced expression via P.IV, whereas the increase in class II expression in the parenchyma of rejecting organs is exclusively due to the activation of the P.IV of CIITA. This result opens possibilities of differentially controlling antigen presentation in different cell types in vivo. Research supported by MRC-PMAC and KFC operating grants.