The major goal of my research program is to understand molecular mechanisms regulating various activities of T cells. Understanding of these mechanisms, particularly those that lead to T-cell activation and inactivation, is expected to facilitate the development of pathways to manipulate TCR signaling and T-cell responsiveness and to develop novel immunotherapeutic interventions to treat viral infections, cancer and other diseases.
Keywords: efficiency of lymphocyte responses, immune receptors and membrane microenvironment, visualization of T cell activation and inactivation
Sykulev, Y. (2010) T cell receptor signaling kinetics takes the stage, Sci Signal. 3: pe50, Epub 2010 Dec 21.
Sykulev, Y. (2010) Changing separating distances between immune receptors as a sensitive mechanism regulating T-cell activation, Self Nonself, 1: 67-68
Mareeva T., Wanjalla, C., Schnell, M. J., and Sykulev, Y. (2010) A novel composite immunotoxin that suppresses rabies virus production in the infected cells, J Immunol. Methods 353: 78-86.
Beal, A.M., Anikeeva, N., Varma, R., Cameron, T.O., Vasiliver-Shamis, G., Norris, P.J., Dustin, M.L., and Sykulev, Y. (2009). Kinetics of early T cell receptor signaling regulate the pathway of lytic granule delivery to the secretory domain. Immunity, 31: 632-642.
Anikeeva, N., Mareeva, T., Liu, W., Sykulev, Y. (2009) Can oligomeric T-cell receptor be used as a tool to detect viral peptide epitopes on the infected cells? Clinical Immunology, 2009 130: 98-109. Epub 2008 Oct 8.
Beal, A. M., Anikeeva, N., Varma, R., Cameron, T. O., Norris, P. J., Dustin, M. L., and Sykulev, Y. (2008) PKC¸ regulates stability of the peripheral adhesion ring junction and contributes to the sensitivity of target cell lysis by CTL. J. Immunol., 181: 4815-24
Mareeva T, Martinez-Hackert E., Sykulev, Y. (2008) How a TCR-like antibody recognizes MHC-bound peptide. J Biol. Chem., 283: 29053-9
Anikeeva, N., Lebedeva, T.,Clapp, A.R., Goldman, E.R., Dustin, M.L., Mattoussi., H., and Sykulev, Y. (2006) QuantumDot/Peptide-MHC Biosensors reveal strong CD8-dependent Cooperation Between Selfand Viral Antigens that Augment the T Cell Response. Proc. Natl. Acad. Sci.USA, 103: 16846-16851.
Anikeeva, N., Martinez-Hackert, E., Kalams, S., Walker, B.D., Hendrickson, W. A. and Sykulev, Y. (2006) Structural basis fordegenerate recognition of natural HIV peptide variants by cytotoxic lymphocytes. J Biol. Chem., 281: 20205-20212.
Lebedeva, T., Dustin, M.L, and Sykulev, Y. (2006) Target cellscontributions to killing through ICAM-1 organization and signaling. In AntigenPresenting Cell (Eds H. Kropshofer & A.B. Vogt), Wiley-VCH, Weinheim, pp.199-206.
Norris,P.J., Stone, J.D., Anikeeva, N., Heitman, J.W., Wilson, I.C., Hirschkorn, D.F.,Clark, M.J., Moffett, H.F., Cameron, T.O., Sykulev,Y., Stern, L.J., Walker, B.D. (2005) Antagonismof HIV-specific CD4+ T cells by C-terminal truncation of a minimumepitope. Molecular Immunology, 43:1349-57.
Lebedeva, T., Dustin, M., and Sykulev, Y. (2005) ICAM-1 co-stimulates target cells facilitating antigen presentation. Current Opinion in Immunology, 17:251-258
Nadia Anikeeva, Kristina Somersalo, Tasha N. Sims, V. Kaye Thomas, Mike L. Dustin and Sykulev, Y. (2005) Distinct role of LFA-1 in effective cytolytic activity of cytotoxic T lymphocytes.Proc. Natl. Acad. Sci. USA, 102: 6437-42.
Lebedeva, T., Anikeeva, N., Kalams, S.A., Walker, B.D., Gaidarov I., Keen, J. H., and Sykulev, Y. (2004) MHC-I-ICAM-1 interactions on the surface of target cells: implication for antigen presentation to cytotoxic T lymphocytes. Immunology, 113: 460-471.
Mareeva, T., Lebedeva, T., Nadja Anikeeva, N., Manser, T. and Sykulev, Y. (2004) Antibody specific for a peptide-MHC complex: is it TCR-like?J. Biol. Chem., 279: 44243-44249.
Somersalo, K., Anikeeva, N., Tasha N. Sims, Verda K. Thomas, Roland K. Strong, Thomas Spies, Lebedeva, T., Sykulev, Y., and Dustin, M.L. (2004) Cytotoxic T lymphocytes form an antigen independent ring junction.J. Clinical Investigation, 113: 49-57.
Anikeeva, N., Lebedeva, T., Kalams, S. and Sykulev, Y. (2003) Soluble HIV-specific T-cell receptor: expression, purification and analysis of the specificity. J. Immunol. Methods, 277: 75-86.
Anikeeva, N., Lebedeva, T., Krogsgaard, M., Tetin, S. Y., Martinez-Hackert, E., Kalams, S., Davis, M.M., and Sykulev, Y. (2003). Distinct molecular mechanisms account for the specificity of two different T-cell receptors. Biochemistry, 42:4709-4716.
Philip J. Norris, Marina Sumaroka, Christian Brander, Howell F. Moffett, Steven L. Boswell, Tam Nguyen, Yuri Sykulev, Bruce D. Walker, Eric S. Rosenberg (2001). Multiple effector functions mediated by HIV-1-specific CD4+ T cell clones. J. Virol., 75: 9771-9779.
Kageyama, S.,. Tsomides, T.J., Fukusen, N., Papayannopoulos, I. A., Eisen, H. N., and Sykulev, Y.(2001).Potent cytolytic response by a CD8+ CTL clone to multiple peptides from the same protein in association with an allogeneic class I MHC molecule. J. Immunol., 166:3028-3034.
Sykulev, Y. (2000). From T-cell receptor ligation to effector functions: affinity, kinetics and pattern recognition. The Immunologist, 9, No 3, 215-221.
Sykulev, Y., Vugmeyster, Y., Brunmark, A., Ploegh, H. L., and Eisen, H.N. (1998). Peptide antagonism and T-cell receptor interactions with peptide-major histocompastibility (MHC) protein complexes.Immunity, 9, 475-483.
Delaney, J., Sykulev, Y., Eisen, H., and Tonegawa, S. (1998). Difference in the level of expression of class I MHC proteins on thymic epithelial and dendritic cells influence the decision of immature thymocytes between positive and negative selection. Proc. Natl. Acad. Sci. USA, 95, 5235-5240.
Eisen, H.N., Sykulev, Y. and Tsomides, T.J. (1996).The antigen-specific T-cell receptors and their reactions with natural ligands: complexes formed by peptides with major histocompatibility complex (MHC) proteins.Adv. Prot. Chem., vol. 49, pp. 1-56, Academic Press, San Diego.
Sykulev, Y., Joo, M., Vturina, I., Tsomides, T.J., and Eisen, H.N. (1996).Evidence that a single peptide-MHC complex on a target cell can elicit a cytolytic T cell response, Immunity, 4, 565-571.
Sykulev, Y.K., Cohen, R.J., and Eisen, H.N. (1995).The law of mass action governs antigen-induced cytolytic activity of CD8+cytotoxic T lymphocytes.Proc. Natl. Acad. Sci. USA,92: 11990-11992
Sykulev, Y., Brunmark, A., Tsomides, T.J., Kageyama, S., Jackson, M., Peterson, P.A., and Eisen, H.N. (1994).High-affinity reactions between antigen-specific T-cell receptors and peptides associated with allogeneic and syngeneic major histocompatibility complex class I proteins. Proc. Natl. Acad. Sci. USA,91: 14487-14491.
Sykulev, Y., Brunmark, A., Jackson, M., Cohen, R.J., Peterson, P.A., and Eisen, H.N. (1994).Kinetics and affinity of reactions between an antigen-specific T-cell receptor and peptide-MHC complexes. Immunity, vol. 1: 15-22.
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