Immunity to T-Cell Receptor: Suppressive Vaccination with DNA Encoding a Variable Region Gene of the T-Cell Receptor

Abstract

A common theme found in studies with mouse models of autoimmune diseases is that pathogenic T cells are primarily responsible for the pathology. Such models include diabetes in non-obese diabetic (NOD) mice, experimental autoimmune encephalomyelitis (EAE)-a model of multiple sclerosis (MS), collagen II (CII)-induced arthritis (CIA)-a model of rheumatoid arthritis (RA). Pathogenic T cells in EAE utilize a restricted repertoire of genes encoding the T-cell receptor (TCR) (1). For example, upon immunization of H-2(u) mice with either myelin basic protein, or its immunodominant fragment, peptide Ac1-20, the Vβ8.2 TCR gene product is expressed in the majority of pathogenic T cells (2-4). The restricted usage of the Vβ8.2 TCR gene product has also been found in rats in which EAE was induced by a peptide of myelin basic protein (5). Similarly, a restriction in the TCR usage was found also in CII-induced arthritis in mice (6,7), and in the TCR alpha chain usage in non-obese diabetic (NOD) mice (8).