Faculty Interests Database

Faculty Affairs: Faculty Interests Database Yuri K. Sykulev, MD, PhD

Microbiology & Immunology
Thomas Jefferson University
Jefferson Medical College
Department of Microbiology and Immunology

Mailing Address Contact Information
233 S 10th Street BLSB706
Philadelphia, Pennsylvania 19107
United States
Phone: 215-503-4530
Fax: 215-923-4153
Expertise and Research Interests
The major goal of my research program is to understand molecular mechanisms regulating various activities of cytotoxic lymphocytes. Understanding of these mechanisms, particularly those that lead to the lymphocyte activation and inactivation, is expected to facilitate the development of novel approaches to manipulate lymphocytes receptor-mediated signaling and their responsiveness and would lead to the development of novel immunotherapeutic interventions to treat viral infections, cancer and other diseases.
Immunobiology of cytotoxic lymphocytes
  • Sykulev, Y. (2010) T cell receptor signaling kinetics takes the stage, Sci Signal. 3: pe50, Epub 2010 Dec 21. (Abstract) (Full Text)
  • 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) Quantum Dot/Peptide-MHC Biosensors reveal strong CD8-dependent Cooperation Between Self and 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.(2005) Structural basis for degenerate recognition of HIV Peptide Variants by Cytotoxic Lymphocytes. J. Biol. Chem., 281: 20205-20212.
  • 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) Antagonism of HIV-specific CD4+ T cells by C-terminal truncation of a minimum epitope. Molecular Immunology, 43:1349-57.
  • Tatiana Lebedeva , Dustin, M., and Yuri Sykulev. Target cells contributions to killing through ICAM-1 organization and signaling. In Antigen Presenting Cell (Eds H. Kropshofer & A.B. Vogt), Wiley-VCH, Weinheim, pp. 199-206.
  • Tatiana Lebedeva , Dustin, M., and Yuri Sykulev (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 Yuri Sykulev (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.
  • 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., 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.
  • Kageyama, S., Tsomides, T.J., Sykulev, Y., and Eisen, H.N. (1995). Variations in the number of peptide-class I MHC complexes required to activate cytotoxic T cell responses. J. Immunol., 154: 567-576.
  • 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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