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.
KeywordsArthritis Electrophoresis Staphylococcus Transferase Mandel
Unable to display preview. Download preview PDF.
- Fukuda M, Horio F, Kubo R, Hattori M (1989) Monoclonal antibody F23.1 against T cell bearing VJS8 TCR elements can prevent the development of insulitis in NOD mice. Diabetes 38 (suppl):12 AGoogle Scholar
- Jorgensen JL, Esser U, Fazekas de St. Groth B, Reay PA, Davis MM (1992) Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics. Nature 355: 224–230.Google Scholar
- Kabat EA, Wu TT, Reid Miller M, Perry HM, Gottesman KS (1987) Sequences of proteins of immunological interest. Department of Health and Human Services, Bethesda, MD, USA, 4th edition.Google Scholar
- Leiter E H (1989) The genetics of diabetes susceptibility in mice. FASEB. J. 3: 2231–2241Google Scholar
- Lund T, O’Reilly L, Hutchings P, Kanagawa O, Simpson E, Gravely R, Chandler P, Dyson J, Picard JK, Edwards A, Kioussis D, Cooke A (1990) Prevention of insulin-dependent diabetes mellitus in non-obese diabetic mice by transgenes encoding modified I–A beta–chain or normal I-E alpha-chain. Nature 345: 727–729PubMedCrossRefGoogle Scholar
- Makino S, Kimimoto K, Muraoka Y, Mizushima Y, Kahagiri K, Tochino Y (1980) Breeding of a non-obese, diabetic strain of mice. Exp. Anim. 1: 1–13Google Scholar
- Waters S H, O’Neil JJ, Melican DT, Appel MC (1992) Multiple TCR V beta usage by infiltrates of young NOD mouse islets of Langerhans. A polymerase chain reaction analysis. Diabetes 41:308–312Webb SR, Sprent J (1990) Response of mature unprimed CD8+ T cells to Mlsa determinants. J. Exp. Med. 171: 953–958Google Scholar