Early evolution of MHC polymorphism

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.