Immunogenetic and immunochemical studies of H-2 antigens of foreign haplotypes on tumour cells.

Abstract

SummaryThe polymorphism of histocompatibility antigens is usually explained by classical Mendelian laws, which allow the inheritance of one allele per locus. Thus each individual would express two antigens for each locus of the pair of relevant homologous chromosomes, one from each parent.Another explanation is that the structural genes of all the different haplotypes are all in tandem. Regulatory genes would then determine the polymorphism by mimicking Mendelian inheritance–allowing only the relevant gene products for a particular haplotype to be expressed. If correct, one might expect the mechanism to fail sometimes, and silent genes of foreign haplotypes to be derepressed, allowing H‐2 antigens of the wrong haplotype to become expressed.In the light of this hypothesis (Martin, 1975; Amos, 1971; Bodmer, 1975; Festenstein, 1978; Garrido et al., 1976a,b), the original findings in our laboratory of extra foreign ‘H‐2‐like’ determinants on tumour cells passaged in vitro and in vivo with and without virus are considered rather important (Festenstein, 1978; Garrido et al., 1976a,b); not only because they could lead to a better understanding of the genetic basis of MHS polymorphism, but also because of its implication for the surveillance of tumours (Garrido et al., 1976b; Gomard et al., 1977; Blank et al., 1976; Parmiani & Invernizzi, 1975) and microbially damaged cells (Doherty & Zinkernagel, 1975). These extra determinants were tested by various serological techniques and assays of cell mediated immunity.