To Study Phosphorylation of CD3 Zeta Chain of T Cell Receptor by Src Kinase

Bandyopadhyay, Debolina (2017) To Study Phosphorylation of CD3 Zeta Chain of T Cell Receptor by Src Kinase. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (MS dissertation of Debolina Bandyopadhyay (12MS032)) Thesis_Debolina_12MS032.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

The structural features of T cell receptor (TCR) CD3 complex play a key role in T cell signaling. The extracellular domain of T cell receptor, which consists of the heterodimers alpha beta subunit, is responsible for recognizing MHC (Major Histocompatibility Complex) molecule. Binding of MHC molecules leads to conformational changes in the TCR:CD3 complex. The cytoplasmic domain of CD3 zeta-zeta homodimer subunit undergoes several conformational changes upon binding of MHC molecule. In resting state the cytoplasmic domain of CD3 zeta and CD3 epsilon subunit remains bound with the inner leaflet of plasma membrane. Upon binding of MHC molecule with the TCR subunit, the cytoplasmic domain of CD3 zeta chain is released from the plasma membrane. The mechanism of release of CD3 zeta chain from the membrane is not known. Once the CD3 zeta chain is released from the membrane, the tyrosine residues of ITAM peptides are exposed for phosphorylation by Lck Kinase. The phosphotyrosine residues act as adaptor to recruit ZAP-70 to the membrane. Recruitment of ZAP-70 to the membrane leads to the activation of kinase domain of ZAP-70 and initiation of downstream signaling. In this thesis, we studied the phosphorylation of CD3 zeta cytoplasmic domain by Src Kinase. There are seven tyrosine residues which are supposed to get phosphorylated by Src Kinase. We ran native gel to check phosphorylation of CD3 zeta chain and at the end of the reaction three species were found.

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