Glassy dynamics in the adaptive immune response prevents autoimmune disease.
The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system's search for antibodies, a balance has evolved between binding affinity and specificity.
Sun
Jun
J
Department of Bioengineering, Rice University, Houston, Texas 77005-1892, USA.
Earl
David J
DJ
Deem
Michael W
MW
D000818:Animals; D000906:Antibodies / Q000737:chemistry; D000941:Antigens / Q000737:chemistry / Q000235:genetics; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control*; D015551:Autoimmunity; D000939:Epitopes / Q000737:chemistry; D019143:Evolution, Molecular; D006801:Humans; D007107:Immune System; D015233:Models, Statistical; D017354:Point Mutation
D000906:Antibodies; D000941:Antigens; D000939:Epitopes