Non-cleavable talin rescues defect in the T-cell conjugation of T-cells deficient in the immune adaptor SKAP1
نویسندگان
چکیده
While the cytoskeletal protein talin binds to the β-chain of LFA-1, the immune cell adaptor SKAP1 (SKAP-55) binds to the α-chain of the same integrin via RapL. Whereas calpain protease cleavage of talin is important for LFA-1 activation, it has been unclear whether SKAP1 can alter the function of talin or its associated adaptor RIAM in T-cells. In this paper, we report that Skap1-/- T-cells showed a reduction in the translocation of talin and RIAM to the contact interface of T-cells with antigenic beads or dendritic cells (DCs) presenting OVA peptide to OT-1 T-cells. In addition, Skap1-/- T-cells show an altered pattern of talin cleavage, while the expression of a cleavage resistant form of talin (L432G) restored the impaired adhesion of OT1 transgenic Skap1-/- T-cells with DCs. SKAP1 therefore can affect the function of talin in T-cells needed for optimal T-cell/DC conjugation.
منابع مشابه
T-cell immune adaptor SKAP1 regulates the induction of collagen-induced arthritis in mice
SKAP1 is an immune cell adaptor that couples the T-cell receptor with the 'inside-out' signalling pathway for LFA-1 mediated adhesion in T-cells. A connection of SKAP1 to the regulation of an autoimmune disorder has not previously been reported. In this study, we show that Skap1-deficient (skap1-/-) mice are highly resistant to the induction of collagen-induced arthritis (CIA), both in terms of...
متن کاملRecent Advances in T Cell Signaling in Aging
The immune system of mammalian organisms undergoes alterations that may account for an increased susceptibility to certain infections, autoimmune diseases, or malignancies. Well characterized are age related defect in T cell functions and cell mediated immunity. Although it is well established that the functional properties of T cells decrease with age, its biochemical and molecular nature is...
متن کاملLFA-1 activates focal adhesion kinases FAK1/PYK2 to generate LAT-GRB2-SKAP1 complexes that terminate T-cell conjugate formation
Lymphocyte function-associated antigen 1 (LFA-1) affinity and avidity changes have been assumed to mediate adhesion to intercellular adhesion molecule-1 for T-cell conjugation to dendritic cells (DC). Although the T-cell receptor (TCR) and LFA-1 can generate intracellular signals, the immune cell adaptor protein linker for the activation of T cells (LAT) couples the TCR to downstream events. He...
متن کاملRegular Article PLATELETS AND THROMBOPOIESIS ADAP interactions with talin and kindlin promote platelet integrin aIIbb3 activation and stable fibrinogen binding
Integrins engage in bidirectional signaling. Fibrinogen binding to integrins is regulated by inside-out signals initiated by agonist receptors, a process often called “integrin activation.” In turn, ligandbound integrins transduce outside-in signals to regulate cellular responses, among them cytoskeletal reorganization. In platelets, integrin aIIbb3 bidirectional signaling is required for effic...
متن کاملDistribution of Circulating Immune Cells in Responder and Non-Responder Individuals to Hepatitis B Vaccine
Unresponsiveness to hepatitis B surface antigen (HBsAg) has been shown to be associated with dysfunction of the presenting cells (APC) and defect in the specific B-lymphocyte and/or T-lymphocyte repertoires. Direct determination of the frequency of specific T-lymphocytes together with complementary analysis of the naive circulating immune cells could provide valuable information about the cel...
متن کامل