An Analysis of T cell receptor diversity in the NOD mouse: What can it tell us about the autoimmune process?
Little is known concerning the features of the T cell receptor (TcR) repertoires which emerge in the course of cell-mediated autoimmune diseases. The finding of a highly restricted variable (V)α or Vβ usage by T cells from animals experimentally induced to respond to self antigens, such as myelin basic protein (MBP) (Acha-Orbea H., 1988) or type 2 collagen (David C.S., 1989, Chiocchia G., 1991), may not necessarily be true for spontaneously-triggered autoimmune reactions. In these reactions, the multiplicity of natural epitopes, the sequential release of sequestered antigens from damaged tissues and the aberrant expression of major histocompatibility complex (MHC) or costimulatory molecules on non-hematopietic cells may contribute to a rapid diversification of V gene usage. The question is important, not only from a theoretical, but also from a practical point of view since many strategies for the prevention of autoimmune diseases by modification of TcR expression are based on the assumption that, for a given individual and a given autoimmune disorder, the T cell repertoire is of sufficiently limited heterogeneity to warrant manipulation.
KeywordsMajor Histocompatibility Complex Class Cell Repertoire Nonobese Diabetic Mouse Versus Beta CDR3 Length
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