Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: April 2, 1996
Publication Date: N/A
Interpretive Summary: Immune response is controlled by many host genes associated with major histocompatibility complex genes (MHC). Class II genes of MHC encode proteins are involved in activating cell-mediated immune responses which are important in host defenses against invading microbial agents including coccidiosis. In this paper, ARS Scientists in collaboration with Iowa State University researchers demonstrate a molecular mechanism involved in T lymphocyte mediated immune response. Particularly, interferon mediated regulation of class II MHC gene expression is demonstrated. This information will increase our understanding of molecular basis for genetic control of immune responses.
A 0.7 kb DNA fragment from the 5' flanking region of a class II beta gene was cloned into the chloramphenicol acetyltransferase (CAT) reporter vectors and was transfected into the MQNCSU chicken macrophage cell line that expresses a low level of MHC class II antigens. Positive orientation-dependent promoter activity of the chicken DNA was evident in a reporter construct containing an SV40 enhancer. Deletion analysis of this 0.7 kb DNA fragment revealed a short fragment in the 3' end that was crucial for the promoter function and negative regulatory elements located further upstream. The conserved MHC class II X and Y boxes did not have a significant influence on promoter activity. Sequence analysis of the 0.7 kb class II beta gene upstream region suggests possible involvement of interferon (IFN), ETS-related proteins, and other factors in regulating this promoter. An IFN-rich chicken T cell line culture supernatent increased surface expression of MHC class II antigens as well as class II beta promoter activity in this macrophage cell line. This first functional characterization of a chicken MHC class II beta gene promoter will aid in understanding the regulatory mechanisms that control the expression of these genes.