TLiSA1 (PTA1) Activation Antigen Implicated in T Cell Differentiation and Platelet Activation Is a Member of the Immunoglobulin Superfamily Exhibiting Distinctive Regulation of Expression

Abstract

T lineage-specific activation antigen 1 (TLiSA1) antigen was initially described as a T lineage-specific activation antigen involved in the differentiation of human cytotoxic T cells. Subsequently, the antigen was identified on platelets and was shown to be involved in platelet activation, hence it was renamed platelet and T cell antigen 1 (PTA1), although identity between the two antigens was not established. In the present study we have cloned the cDNA encoding TLiSA1 from Jurkat cells and show it to be a novel member of the immunoglobulin superfamily with the unusual structure of two V domains only. Identity between TLiSA1 and platelet PTA1 is established by immunological criteria, by internal peptide sequences obtained from the purified platelet glycoprotein and by sequencing the platelet transcript after reverse transcriptase-polymerase chain reaction. In Jurkat cells, TLiSA1/PTA1 mRNA and surface protein expression is greatly stimulated by treatment of the cells with phorbol ester, but the T cell proliferative signal of phorbol ester and ionophore combined greatly reduces or abrogates this response, and this suppressive effect of the ionophore is not reversed by incorporating FK506 to inhibit calcineurin. Together with the known signaling role of PTA1, these data substantiate the notion that this molecule is implicated in T cell differentiation, perhaps by engagement of an adhesive ligand.

The LFA-1-associated Molecule PTA-1 (CD226) on T Cells Forms a Dynamic Molecular Complex with Protein 4.1G and Human Discs Large

“…PTA-1 cDNA was subcloned into the high expression level eukaryotic vector, pEF-BOS, as described previously (54). The permanent Jurkat-PTA-1 cell line was established using the LipofectAMINE™ 2000 reagent (Invitrogen) to introduce a 10:1 excess of the pEF-BOS-PTA-1 vector (which lacks a eukaryotic selection marker) to pREP9 (which encodes neomycin phosphotransferase; Invitrogen), followed by selection with 750 g/ml G-418 (Invitrogen).…”

“…PTA-1 (also known as CD226, TLiSA-1, and DNAM-1) is a member of the immunoglobulin superfamily, the expression of which is regulated by phorbol ester and calcium (53,54). Initially identified as a T cell activation antigen, antibodies and F(abЈ) 2 fragments against PTA-1 inhibit the development of cytotoxic T cells and T cell clones from their precursors (55)(56)(57).…”

Expression of CD226 Antagonizes Apoptotic Cell Death in Murine Thymocytes

“…T he CD226, also named TliSA1, PTA1, or DNAM-1, is a member of the Ig superfamily containing two Ig V-like domains in its extracellular region and three tyrosine residues in its cytoplasmic portion (1,2). In humans, CD226 is constitutively expressed in hematopoietic cells such as T cells, NK cells, NKT cells, a subset of B cells, monocytes/macrophages, and dendritic cells and is involved in a variety of immunological functions, including T cell differentiation and cytotoxicity, NK cell cytotoxicity, NKT cell apoptosis, monocyte extravasation, and dendritic cell maturation (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

Interaction of cancer cells with platelets mediated by Necl-5/poliovirus receptor enhances cancer cell metastasis to the lungs

“…Initiation of the cytotoxicity function by cross-linking of the CD226 receptor depends upon its Ser329 phosphorylation by protein kinase C (PKC) and physical and functional interactions with LFA-1 (Shibuya et al, 1999). CD226 is also known as platelet and T-cell antigen 1 and its cross-linking by a mAb stimulates platelet secretion and activation in a PKC-dependent manner (Sherrington et al, 1997). On the other hand, Necl-5 colocalizes with integrin a v b 3 at the leading edges of moving cells and enhances growth factor-induced cell movement and proliferation by facilitating growth factor-induced activation of Cdc42 and Rac small G proteins Kakunaga et al, 2004).…”