Yuri Sykulev, M.D., Ph.D.


Professor
Microbiology & Immunology

Telephone
215-503-4530

Office Address
706 BLSB
233 S. 10th St.

Email Address
ysykulev@mail.jci.tju.edu

 

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
 

PubMed Link For Sykulev Y


Selected Publications

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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