title: Adaptive value of polymorphism in intracellular self/not-self discrimination?
abstract: A microbial pathogen species can adapt to its host species to the extent that members of the host species are uniform. Loss of this uniformity would make it difficult for a pathogen species to transfer, from one member of the host species to another, what it had "learned" through selection of its members with advantageous mutations. The existence of major histocompatibility complex (MHC) polymorphism indicates that non-uniformity within a species is an effective host defence strategy. By virtue of this molecular discontinuity among its members the host species can "present a moving target" to the pathogen. Many proteins other than MHC proteins show polymorphism - a phenomenon which has suggested that mutations in regions of protein molecules which do not affect overt function are neutral. However, in the context of the author's differential aggregation theory of intracellular self/not-self discrimination as previously applied to the problem of the antigenicity of cancer cells, such polymorphism should serve for the recruitment of subsets of self-antigens into the antigenic repertoire of an infected cell. These would act as "intracellular antibodies" by virtue of their weak, but specific, aggregation with pathogen proteins. Peptides from the self-antigens, as well as (or instead of) those from the antigens of the pathogen, would then serve as targets for attack by cytotoxic T cells. Thus, polymorphism of intracellular proteins should be of adaptive value, serving to amplify and individualize the immune response to intracellular pathogens.
authors.affiliation: Department of Biochemistry, Queen's University, Kingston, Ontario, K7L 3N6, Canada. forsdyke@post.queensu.ca
authors.forename: D R
authors.initials: DR
authors.lastname: Forsdyke
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology; D018448:Models, Immunological; D009369:Neoplasms / Q000276:immunology*; D011110:Polymorphism, Genetic; D017634:Self Tolerance; D014764:Viral Proteins / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
chemical_list: D000941:Antigens; D008565:Membrane Proteins; D014764:Viral Proteins