Immunological tolerance for the diverse antigen binding domains of B cell and T cell receptors

Abstract

The semi-random generation of lymphocyte receptor binding domains through V(D)J recombination creates a vast repertoire of receptors to combat pathogens. Establishing tolerance towards these receptors requires an equally vast repertoire of self-antigens. How is this repertoire established and what is its impact on the negative selection process? This review attempts to create an overview of self-antigen repertoires in the humoral immune system, with a focus towards B cell receptors and T-cell receptors. It establishes the possible roles and mechanisms of tissue restricted antigen regulators like AIRE, as well as the role of B-1 cells in this process. It also includes a brief overview of peripheral tolerance and its impact in this context. The final conclusion is that tolerance towards T-cell receptors seems incomplete, but the lack of relevant diseases indicates an as of yet undiscovered T-cell receptor repertoire.