Function of the Lck and Fyn in T cell development

Abstract

The development of T cell in the thymus and the activation of mature T cells in the secondary lymphoid tissues require T cell to make adaptive responses to signaling molecules of environment. The activation of T cell receptor (TCR) signaling pathway could be induced by the interaction of the TCR and its co-receptor CD4 and CD8 with MHC/peptide complex. This process involves co-stimulatory molecules and signals mediated by cytokine receptors, which eventually leads to the occurrence of T cell immune response. The Src-family kinases lymphocyte-specific protein tyrosine kinase (Lck) and proto-oncogene tyrosine-protein kinase (Fyn) are expressed in T cells and serve as the signaling molecules that are activated downstream of TCR. These signaling molecules play key roles in development, positive selection, and peripheral maintenance of naive T cells and lymphopenia-induced proliferation of peripheral T cells. Both Lck and Fyn are required for each of these TCR-based signaling pathways, and Lck seems to be the major contributor, while Fyn can only supplement some functions of Lck. In this review, we discussed the mechanisms by which these two proteins perform functions in T cell development based on our current understanding.

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“…Such T lymphocoytes could be distinguished by the expression of mutually exclusive CD4 + or CD8 + co-receptors ( 38 ). Additionally, Lck is a cytoplasmic protein bound to CD4 and CD8 in T cells, which participates in antigen-induced T cell activation ( 39 ). Here, in the present study, the expression of tcra, tcr β , lck , and cd8 also showed no significant difference between two groups, which indicated that dietary CPC inclusion did not significantly affect the expression of T cell markers.…”

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“…The T cell response is initiated following engagement of the T cell receptor (TCR) and CD4 or CD8 co-receptors by cognate antigen/MHC complexes presented by macrophages or other antigen-presenting cells [124,125]. TCR stimulation is immediately followed by tyrosine phosphorylation of composite protein structures known as immunoreceptor tyrosine-based activation motifs (ITAMs), which are located in the cytoplasmic domains of protein subunits which constitute the TCRassociated CD3 complex [126].…”

“…This phosphorylation is enabled by activation of the src-family kinases lymphocytespecific protein tyrosine kinase (Lck) and, to a lesser extent, proto-oncogene tyrosine protein kinase (Fyn). The activation of these kinases and the physical interaction with protein chains of the CD3 receptor are a crucial element in TCR signalling activation [124,125]. This phosphorylation of ITAM acts to recruit the ZAP-70 tyrosine kinase normally located in the cytosol to the plasma membrane, whose main substrate is the transmembrane protein LAT otherwise described as linker for activation of T cells [28,126].…”