Adaptive value of polymorphism in intracellular self/not-self discrimination?

A microbial pathogen species can adapt to its host species to the extent th at members of the host species are uniform. Loss of this uniformity would m ake 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 me mbers with advantageous :mutations. The existence of major histocompatibili ty complex (MHC) polymorphism indicates that non-uniformity within a specie s is an effective host defence strategy. By virtue of this molecular discon tinuity 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 molecul es which do not affect overt function are neutral. However, in the context of the author's differential aggregation theory of intracellular self/not-s elf discrimination as previously applied to the problem of the antigenicity of cancer cells, such polymorphism should serve for the recruitment of sub sets of self-antigens into the antigenic repertoire of an infected cell. Th ese would act as "intracellular antibodies" by virtue of their weak, but sp ecific, 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 a nd individualize the immune response to intracellular pathogens. (C) 2001 A cademic Press.