Analysis of biological roles of class II major histocompatibility antigen by anti-sense RNA

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We have established an anti-sense RNA system which is capable of regulating the expression of the endogenous class II MHC (la) molecule in order to elusidate the role of la molecules on immune responses. The 100 base pairs of the l-A chain gene were constructed under the control of a metallothionein gene promoter in an anti-sense orientation. This anti-sense gene was taransfected into the la^+ B lymphoma cells. The amount of la molecules on the transfectants was specifically reduced to less than 5% of the control level. The rations of the amount of anti-sense and sense mRNA in the transfectants correlated with the amount of the la molecules, indicating that the duplex fomation of sense and anti-sense RNA inhibits translation of the sense mRNA. Antigen presenting cell activities of the transfectants to the la restricted T cells also correlated with the amount of la molecules.simultaneously, this anti-sense gene was microinjected into fertilized eggs of C57BL/6xSJL F1 mice to raise the transgenic mice. In these transgenic mice, 1)the amount of la molecules on the spleen cells was distinctly reduced, 2) anti-sense rna was detected in total RNA from spleen cells of the transgenic mice. We are examining immune abnormalities of these mice.