Defectos en la síntesis de cadena ζ en el linfocito T, generando señales intracelulares equivocadas, responsables de lupus eritematoso sistémico / Defects in the synthesis of ζ chain in T lymphocytes, generating wrong intracellular signals, responsible for systemic lupus erythematosus

La expresión anormal de moléculas claves en señalización y la función defectuosa de los linfocitos T cumplen un papel significativo en la patogénesis de la enfermedad autoinmune. Las células T muestran numerosas anormalidades en la señalización del complejo TCRζ¹, estas aberraciones resultan en la alteración de la expresión de citoquinas. Mientras algunas de estas anormalidades explican el aumento de la actividad de células B por células T con incremento de los anticuerpos, la disminución en la producción de IL-2 resulta en un aumento en la susceptibilidad a las infecciones, reducción en la activación de las células T, inducción de la muerte celular y prolongada sobrevida de las células T autorreactivas².

The abnormal expression of key molecules in signaling and the malfunction of the T cell T have a significant activity in the pathogenesis of the autoimmune disease. The cells T exhibit numerous abnormalities in the signaling of the complex TCRζ¹, these aberrations result in the alteration of the citoquines. While some of these abnormalities explain the increase of the activity of cells B for cells T with increment of the antibodies production, the decrease in the production of IL-2 induces an increase in the susceptibility to the infections, diminishing in the activation of the cells T, and expansion of the lifespan of the autorreactive cells².

Molecular Cloning of Human 14-3-3 cDNA with CD3 Zeta Peptide Containing Phosphosering Tag / 대한면역학회지

14-3-3 proteins are highly conserved proteins of about 29 kDa and have a minimum of seven isoforms. 14- 3-3 proteins interact with many signalling proteins by the recognition of phosphoserine. For the identification of proteins which react with ITAM (immunoreceptor tyrosine-based activation motif) of CD3 zeta chain, labeled synthetic peptides representing the CD3 zeta chain structual motifs (ITAMs) with a tag of PKC substrate sequence were used for western blotting. One major protein band of approximately 29 kDa was identified in lysate of Jurkat T cell, B cells and HeLa cells. Screening of lamda gt 11 library derived from HeLa cell gave two clones of 14-3-3 protein cDNA. Inspection of their nucleotide sequences identified these two full length cDNA clones as the 29 kDa human homologue of rat 14-3-3 gamma and the human 14-3-3 zeta protein. The human 14-3-3 gamma isoform also showed high homology with other species in amino acid and nucleotide sequence. Although 14-3-3 proteins are phosphoserine-binding proteins, there may be another way of interaction between ITAMs of CD3 and 14-3-3 proteins.