T Cell Signal Transduction and the Role of CD7 in Costimulation

Abstract

The complex cellular interactions that govern the mammalian immune response are now known to include specific receptor/ligand interactions, recruitment of intracellular signaling molecules, activation of both kinases and phosphatases, and redistribution of macromolecular complexes into specific subcellular membrane locations that, in aggregate, result in transcriptional activation. While the TCR-CD3 signal is critical for activation of the resting T cell, it alone is not sufficient to initiate transcriptional activation or generate an effective immune response. A number of other coreceptor molecules, including CD4, CD8, and CD28, have now been characterized that also play important roles in initiating or amplifying the activation of the T cell. A 40 kDa member of the immunoglobulin superfamily, the CD7 molecule, has also been shown to have costimulatory activity and to induce tyrosine and lipid kinase activities. Here we will review the signaling pathways initiated by TCR, CD28, and CD7, as well as the functional consequences of signal transduction through these receptors.

Identification of Distinct Gene Expression Profiles between Esophageal Squamous Cell Carcinoma and Adjacent Normal Epithelial Tissues

“…CD7 is a cell surface glycoprotein member of the immunoglobulin superfamily and is found on thymocytes and mature T-cells. It plays an essential role in T-cell and T-cell/B-cell interactions during early lymphoid development (Stillwell and Bierer 2001). It has been reported that CD7 expression is up-regulated in chronic myeloid leukemia (CML) cells and in other leukemias and lymphomas (Rogers et al 2010).…”

CD99 activates T cells via a costimulatory function that promotes raft association of TCR complex and tyrosine phosphorylation of TCR ζ

“…Among the known costimulatory molecules, CD28 launches the most effective activation of T cells (Alegre et al, 2001;. However, recent reports have suggested that many other candidates, most of which reside in the lipid raft, induce T-cell activation as potently as CD28 does (Denning et al, 1988;Ledbetter et al, 1988;Green et al, 1994;Tai et al, 1996;Yashiro-Ohtani et al, 2000;Stillwell and Bierer, 2001).…”

“…Among the known costimulatory molecules, CD28 launches the most effective activation of T cells (Alegre et al, 2001;. However, recent reports have suggested that many other candidates, most of which reside in the lipid raft, induce T-cell activation as potently as CD28 does (Denning et al, 1988;Ledbetter et al, 1988;Green et al, 1994;Tai et al, 1996;Yashiro-Ohtani et al, 2000;Stillwell and Bierer, 2001).The lipid raft is a unique membrane microdomain that is enriched with specific types of lipids and cholesterol and is associated with many key molecules involved in TCR signaling. Upon engagement of cognate ligands (peptide/MHC), TCRs are recruited toward the raft along with a series of tyrosine-phosphorylated signaling molecules (Moran and Miceli, 1998;Xavier et al, 1998;Janes et al, 1999).…”

Expansion of CD7low and CD7negative CD8 T-cell effector subsets in HIV-1 infection: correlation with antigenic load and reversion by antiretroviral treatment

“…27 CD7 has been recognized as a costimulatory molecule, leading to increased integrin adhesiveness through activation of phosphatidylinositol 3 (PI3) kinase. [28][29][30][31] Interestingly, CD7 is also necessary for induction of apoptosis in T cells by the ␤-galactoside-binding lectin galectin-1. 32-36 CD7 may thus play contrasting roles during different stages of an immune response.…”