Viral Superantigens in Mice and Humans

Abstract

Adaptive immunity relies on the antigen-specific B cell (BCR) and T cell (TCR) receptors to survey for pathogenic events. Upon recognition of a microbe by these receptors, an immune response is initiated, resulting in the differentiation of the antigen-specific lymphocytes into effector cells, which eliminate the pathogen. According to the IMGT database, there are 23 and 18 functional T cell (TCR) receptors Vβ-families in humans and mice, respectively. The majority of known superantigens (SAgs) are of either bacterial or viral origin, the prototypes being the bacterial pathogens Staphylococcus aureus and Streptococcus pyogenes and the murine mammary tumor virus (MMTV). While the exogenous virus encoded SAg is critical for the viral infection, the expression of endogenous MMTV SAgs leads to thymic deletion of T cells with the corresponding Vβ-chains, hence rendering the mice resistant to infection by exogenous MMTV encoding SAgs with the same Vβ specificity. During thymic maturation, only T cells that receive signals above a certain threshold survive by undergoing positive selection. Expression of a strong endogenous SAg during the negative selection process often results in thymic deletion of the entire population of T-cell expression TCR Vβ-chains that are reactive to the SAg, while a weak SAg activity leads to partial deletion or anergy of the reactive T cells.