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

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. Aβ4^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.