T cells are central in immune responses to a variety of pathogens including bacterial, viral and protozoan infections. Hyperactivation of T cells targeted at 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 allows tumors to grow unchecked. Secondary to the wide variety of different physiologic and pathophysiologic states in which T cell have been implicated, it is of great interest to be able to track and modulate antigen-specific T cells.

Current technology for identifying/isolating antigen-specific T cells is crude. Recently, using immunoglobulin as a molecular scaffold, we have constructed soluble divalent analogs of MHC and TCR molecules ligands (called MHC and TCR superdimers) that have high affinity for their cognate ligands. Ongoing projects analyze the use of MHC and TCR superdimers to track and modulate immune responses in vitro and in vivo. Specifically these novel compounds are being used to study autoimmune diseases such as MS and diabetes as well as immunotherapy for cancer. Insights gained from these studies will provide novel approaches for immune-based therapeutics.

Oelke M, Krueger C, Giuntoli RL II, Schneck JP. (2005) Artificial antigen-presenting cells: artificial solutions for real diseases. Trends in Molecular Medicine 55(3):594-602 [PubMed]

Oelke M, Maus MV, Didiano D, June CH, Mackensen A, and Schneck JP. (2003) Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig coated artificial Antigen Presenting Cells. Nature Medicine 125(47):14596-602 [PubMed]

Brehm MA, Pinto AK, Daniels KA, Schneck JP, Welsh RM, Selin LK. (2002) T cell immunodominance and maintenance of memory regulated by unexpectedly cross-reactive pathogens. Nat. Immunol. 11(8):1015-23 [PubMed]

Fahmy, T., Bieler, J.G., Edidin, M., and Schneck, J.P. (2001) Increased TcR avidity after T cell activation: A mechanism for sensing low density antigen. Immunity 276(11):7701-4 [PubMed]

Hamad AR, Srikrishnan A, Mirmonsef P, Broeren CP, June CH, Pardoll D, Schneck JP. (2001) Lack of coreceptor allows survival of chronically stimulated double-negative alpha/beta T cells: implications for autoimmunity. J. Exp. Med. 21(14):4837-46 [PubMed]

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. P. (1998) Direct visualization of antigen-specific T cells: HTLV-1 Tax11-19- specific CD8(+) T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients. Proc. Natl. Acad. Sci. USA 16(2):235-40 [PubMed]

O'Herrin, S. M., Lebowitz, M. S., Bieler, J. G. , Al-Ramadi, B., Utz, U., Bothwell, A., and Schneck, J. (1997) Analysis of the expression of peptide-major histocompatability complexes using high affinity soluble divalent T cell receptors. J. Exp. Med. 279(8):7331-8 [PubMed]