Jonathan P. Schneck, M.D., Ph.D.

Co-Investigator, Project 4 and

Developmental Research Program

Professor,
Department of Medicine

Department of Pathology

Room 664-G
Ross Research Building

410-614-4589
410-614-3548 (Fax)

jschneck@jhmi.edu

http://www.pathology2.jhu.edu/schnecklab

Research Interests: 

T cell responses:  From recognition to regulation

Antigen specific T cells play major roles in both normal physiologic immune responses as well as in many disease states.  T are central in the immune response to a variety of pathogens including bacterial, viral and protozoan infection.  Hyperactivation of antigen specific T cells targeted toward self antigens is the underlying basis for the majority of autoimmune diseases including: multiple sclerosis, arthritis and diabetes.  Conversely, inactivity of tumor antigen-specific T cells may allow tumors to grow.  Secondary to a wide variety of different p0hysiologic and pathophysiologic responses in which T cells are implicated, it is of great interest to be able to track and modulate antigen-specific T cells which will lead to better insights into therapeutic selective immunomodulation for both autoimmune diseases and cancer.

Current technologies for identifying/isolating antigen-specific T cells have dramatically advanced by the development of soluble multivalent MHC analogs.  Recently, using immunoglobulin as a molecular scaffold, we have constructed soluble divalent analogs of MHC and TCR molecules ligands (called MCH and TCR superdimers) that have high affinity for their cognate ligands.  The divalent nature of the analog effectively increases the affinity of the complex allowing for stable binding to antigen-specific T cell receoptors.  Our lab focuses broadly on probing T cell responses and antigen-processing uding the MHC-Ig reagents developed by the group.

Selected Publications

Schneck, J., Maloy, W.L., Coligan, J.E., and Margulies, D.H., Inhibition of an allospecific T cell hybridoma by soluble class I proteins and peptides: Estimation of the affinity of a T cell receptor for class I MHC molecules.  Cell, 55, 47-53, 1989.

Hamad, A.R.A., O’Herrin, S., Lebowitz, M., Srikrishnan, A., Bieler, J., Schneck, J., and Pardoll, D., Potent T Cell Activation with Dimeric Peptide-MHC Class II Ligand: The Role of CD4 Coreceptor, JEM, 188: 1633-1640, 1998.

Greten, T.F., Slansky, J.E., Kubota, R., Soldan, S.S., Jaffee, E.M., Leist, T.P., Pardoll, D.M., Jacobson, S., and Schneck, J., Direct visualization of antigen-specific T cells: HTLV-1 Tax 11-19 specific CD8+ T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients, PNAS, 95: 7568-7573, 1998.

Howard, M., Spack, E.G., Choudhury, K., Greten, T.F., and Schneck, J., The Major Histocompatibility Complex Leads the Way for Disease-Linked into the Clinic, Immunol. Today, 20: 161-165, 1999.

Marguet, D., Spiliotis, E.T., Pentcheva, T., Lebowitz, M., Schneck, J., and Edidin, M., Lateral Diffusion of GFP-Tagged H2Ld Molecules and of GFP-TAP 1 Reports on the Assembly and Retention of these Molecules in the Endoplasmic Reticulum, Immunity, 11: 231-240, 1999.

Fahmy TM, Bieler JG, Edidin M, Schneck JP. Increased TCR avidity after T cell activation: a mechanism for sensing low-density antigen. Immunity. 2001 Feb;14(2):135-43.