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Early evolution of MHC polymorphism
1Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Abstract:
There is unwarranted satisfaction with the view that MHC polymorphism evolved because there was a selective advantage in having a variety of MHC proteins to bind a variety of peptide subsets for presentation to T cells. While this may, in part, explain its maintainance, polymorphism may have evolved initially to reject foreign virus "grafts". The possession of similar membranes promotes aggregation between "like" cells, but it also promotes aggregation between the cells and viruses which retain membrane components of their previous host. The selection pressure afforded by hostile virus "grafts" would favour cells which developed polymorphic membrane components (since "like" will not aggregate with "not-like"). This polymorphism would have evolved before the appearance of multicellular organisms. Thus, the evolution of modern immune systems would have been imposed upon pre-existing polymorphic systems. A path this evolution may have taken involves the development of mechanisms for intracellular distinction between self and not-self.
Insights
Major histocompatibility complex (MHC) polymorphism may have initially evolved to reject viral "grafts," not just peptide presentation. This ancient defense mechanism predates multicellularity, influencing modern immune system evolution.
Area of Science:
- Immunology
- Evolutionary Biology
- Molecular Biology
Background:
- The prevailing view attributes Major Histocompatibility Complex (MHC) polymorphism to the advantage of presenting diverse peptide subsets to T cells.
- This explanation may account for the maintenance of MHC diversity but not necessarily its initial evolution.
Purpose of the Study:
- To propose an alternative hypothesis for the initial evolution of MHC polymorphism.
- To explore the role of viral "grafts" as a selective pressure driving MHC polymorphism before the advent of multicellularity.
Main Methods:
- Theoretical modeling of molecular interactions.
- Comparative analysis of evolutionary pressures on cell membranes.
- Hypothesizing evolutionary pathways for immune system development.
Main Results:
- MHC polymorphism may have evolved as a defense mechanism against viruses that incorporate host cell membrane components.
- Similar membrane components can cause self-cell aggregation and also aggregation with viruses, creating a selective pressure.
- Selection favors cells with polymorphic membrane components to prevent aggregation with "non-like" entities, including virus grafts.
Conclusions:
- MHC polymorphism's origins might lie in rejecting foreign viral "grafts" rather than solely in peptide presentation.
- This ancient polymorphism predates multicellular organisms and likely influenced the subsequent evolution of modern immune systems.
- The development of self/non-self distinction mechanisms in immune systems may have been imposed upon pre-existing polymorphic systems.