T-cell surface glycoprotein CD3 epsilon chain (CD3e) and gamma chain (CD3g) are components of the TCR-CD3 complex present on T-lymphocyte cell surface, playing a crucial role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted through the cell membrane via CD3 chains including CD3d, CD3e, CD3g and CD3z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, leading to downstream signaling pathway activation. Additionally, CD3e is essential for correct T-cell development as it initiates the TCR-CD3 complex assembly by forming two heterodimers CD3d/CD3e and CD3g/CD3e. CD3e also participates in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3e cytosolic region. Mutations in CD3e result in severe combined immunodeficiency (SCID). On the other hand, CD3g plays an essential role in dynamic regulation of TCR expression at the cell surface. Constitutive TCR cycling is dependent on the di-leucine-based (diL) receptor-sorting motif present in CD3g. Deficiencies in CD3g can impair immune function, particularly in Treg cells which may contribute to autoimmune disorders.