Superantigen-Like Effects and Incidence of Diabetes in NOD Mice

Abstract

The population of T-cells that develops in any individual can be divided into families based on sequence differences in the β-chain variable region of the T-cell receptor heterodimer. Major histocompatibility complex products and endogenous retroviral gene products have both been shown to exert powerful influences on the frequency distribution of T-cell receptor β-chain variable region families in the mouse. In most mouse strains, these repertoire modifiers appear to be fully functional early in mouse development and shape a repertoire of antigen specificities that remains essentially unchanged from the first weeks of life until old age. In NOD mice, an inbred mouse model of type I diabetes, puberty in males coincides with a β-chain variable region-specific T-cell expansion that mimics the results of exposure to exogenous superantigens in immunologically mature animals. The subsequent behavior of this subset indicates that it may play a role in the relative protection of male NOD mice from complete pancreatic β-cell destruction and overt diabetes.