Sublocalization on chromosome 21 of human interferon-alpha receptor gene and the gene for an interferon-gamma response protein

Abstract

The cellular responses to alpha and beta interferons (IFN-alpha and -beta) are mediated through the IFN-alpha/beta (type I) receptor, while the response to IFN-gamma is mediated through the IFN-gamma (type II) receptor. The receptors for IFN-alpha/beta and IFN-gamma are encoded by genes on human chromosomes 21 and 6q, respectively. The presence of chromosome 21q confers both ligand binding and responsiveness to human IFN-alpha/beta, whereas chromosome 6q confers binding of Hu-IFN-gamma, but not cellular responsiveness on somatic cell hybrids. Chromosome 6q (i.e., the Hu-IFN-gamma receptor gene) and chromosome 21q are both necessary for the cellular response of somatic cell hybrids (from fibroblasts) to Hu-IFN-gamma. It is conceivable that the factor mediating activity through the IFN-gamma receptor is, in fact, the IFN-alpha receptor, or that the two genes are distinct but part of an "interferon response" region. Here we more precisely localize on human chromosome 21 the genes for the IFN-alpha receptor and for the factor(s) mediating the action of IFN-gamma through the chromosome 6-encoded receptor. Hamster-human somatic cell hybrids containing various fragments of human chromosome 21 were used. The presence of the human IFN-alpha/beta receptor was determined by binding 32P-labeled human IFN-alpha to cells, covalently cross-linking the [32P]IFN-alpha-receptor complex, and analyzing it by SDS-polyacrylamide gel electrophoresis. The presence of the IFN-gamma receptor-related factor mediating cellular responsiveness was determined by HLA induction in hybrid cells containing the IFN-gamma receptor (chromosome 6q), a transfected copy of the human HLA-B7 gene, and various portions of chromosome 21. In all hybrids examined, the two genes cosegregate. Specifically, both genes are localized to the region of chromosome 21 containing the markers D21S58, D21S65, and GART and appear to be proximal to D21S58. The implications for IFN action are discussed.