Hidden variables: unstable Aβ chain genes encoding antigen recognition structures in tumor survivors

Abstract

Novel single exon genes Aβ4-7 comprising the Aβ6 gene family have been cloned from mouse mutants surviving transplantable metastatic tumors. Their protein coding sequences are similar to H2-Ab cDNA which encodes antigen-binding molecules of antigen presenting cells (APC); their promoters and/or signal sequences are unrelated to Ab sequences but found in other eukaryotic genes. A β4 b protein was demonstrated on macrophages and B cells that are APC. The Aβ6 w302 appears to be an ancient gene ancestral to major histocompatibility complex (MHC) class II β genes. However, unlike the MHC class II, the Aβ4-7 genes are not involved in skin graft rejection. Despite inbreeding, the Aβ6 w302 locus remains unfixed in several strains of mice. The number of Aβ genes and their alleles varied between individual mice; they do not map into the H2 region but appear to be scattered over the genome. The Aβ6 gene family is molecularly unstable in Aβ6 w302 -positive (but not in Aβ6 w302 -negative) mice which are somatic mosaics for these genes. Biological features of Aβ4-7 genes make them remarkably different from the classical MHC gene system. All available evidence strongly suggests that these genes control susceptibility/resistance to the spread of metastatic tumors.