Abnormal tyrosine phosphorylation on T-cell receptor in lymphoproliferative disorders

Nature. 1986 Dec 18-31;324(6098):674-6. doi: 10.1038/324674a0.

Abstract

The study of human autoimmune diseases has benefited greatly from analysis of animal models. Mice that are homozygous for either the lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) mutant genes develop a disease characterized by massive lymphadenopathy and autoantibody formation. With age, the lymphoid organs in these mice are replaced with a greatly expanded population of abnormal lymphocytes. Recent work has shown that these cells are likely to be in the T-cell lineage. They rearrange and transcribe the genes for the alpha and beta subunits of the T-cell receptor (TCR) and a third, T-cell receptor-like gene, T gamma. As determined by immunofluorescence with anti-receptor antibodies the cells also express TCR on the cell surface. The murine T-cell receptor consists of the alpha and beta chains, derived from the rearranged alpha and beta genes, in non-covalent association with seven other chains; the delta chain, of relative molecular mass (Mr) 26,000 (26K), the epsilon chain (25K), a glycosylated 21K chain (gp21) which is probably the homologue of the gamma chain of T3 (CD3), a 16K homodimer (zeta) and a 21K dimer (p21). This multichain complex is thought to be the murine analogue of the human T3 complex. After activation of normal T cells by antigen or lectin, p21 is phosphorylated on tyrosine residues and gp21 is phosphorylated on serine residues. In contrast, in the gld and lpr cells, p21 is phosphorylated even in the absence of antigen or lectin, whereas gp21 is not phosphorylated.

MeSH terms

  • Amino Acids / analysis
  • Animals
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / immunology*
  • Macromolecular Substances
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Phosphorylation
  • Phosphotyrosine
  • Receptors, Antigen, T-Cell / isolation & purification*
  • Receptors, Antigen, T-Cell / metabolism
  • Tyrosine / analogs & derivatives*
  • Tyrosine / analysis

Substances

  • Amino Acids
  • Macromolecular Substances
  • Receptors, Antigen, T-Cell
  • Phosphotyrosine
  • Tyrosine