Autoimmunity and the microbiome: T-cell receptor mimicry of "self" and microbial antigens mediates self tolerance in holobionts: The concepts of "holoimmunity" (TcR-mediated tolerance for the holobiont) and "holoautoimmunity" (loss of tolerance for the holobiont) are introduced.
I propose a T-cell receptor (TcR)-based mechanism by which immunity mediates both "genetic self" and "microbial self" thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross-reactivity with "self," resulting in selection for a TcR repertoire mimicking "genetic self." Second, evolution has selected for a "microbial self" that mimics "genetic self" so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel mechanism for modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR-microbiome mimicry "holoimmunity" to denote immune tolerance to the "holobiont self." Logically, microbiome-host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross-react with host antigens producing "holoautoimmunity."
Michigan State University, East Lansing, MI, USA. rootbern@msu.edu.
Robert
R
Root-Bernstein
D015551:Autoimmunity; D006801:Humans; D007108:Immune Tolerance; D064307:Microbiota / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell
Crohn's disease; T-cell receptors; antigenic mimicry; autoimmunity; diabetes; holobiont; immune tolerance; immunologic mimicry; microbiome; non-self