REGULATION OF TRANSGENIC CLASS-II MAJOR HISTOCOMPATIBILITY GENES IN MURINE LANGERHANS CELLS

I-E is a class II major histocompatibility complex molecule normally e xpressed by Langerhans cells, A series of transgenic mice were develop ed previously that carry E(alpha)(d) gene constructs with promoter-reg ion deletions that cause expression of I-E by different cell types whe n maintained bn a B6 (I-E[-]) genetic background, To study cis-acting gene sequences that regulate expression of class II proteins by Langer hans cells, we identified transgenic I-E expression by tissue immunope roxidase staining and by epidermal cell suspension immunofluorescence cytometry. Mice with a transgene containing 1.4 kilobase pairs (kb) of flanking sequence 5' to the E(alpha) initiation site expressed barely detectable levels of I-E on a tiny percentage of Langerhans cells, in dicating that sequences promoting Langerhans cell expression of E(alph a) exist between 2.0 and 1.4 kb 5' of the E(alpha) initiation site. Re moval of an additional 170 bp of 5' flanking sequence caused near-norm al levels of expression by approximately one third of epidermal Langer hans cells, which contrasts with studies that showed minimal transgene expression by,splenic dendritic cells in these animals. Thus, sequenc es between 1.4 and 1.23 kb 5' of the E(alpha) initiation site decrease expression of I-E by epidermal Langerhans cells, but enable I-E expre ssion by splenic dendritic cells, These studies identify Langerhans ce ll-specific regulatory sequences and genetic regions controlling major histocompatibility complex class II gene expression in Langerhans cel ls and splenic dendritic cells, The genetic regions identified may be particularly important because differential regulation of class II maj or histocompatibility complex protein synthesis by Langerhans cells an d dendritic cells may be crucial to immune functions of intact animals .