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Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

Research Focus

Structural Studies of T Cell Functions and Dysfunction

My laboratory is trying to elucidate the molecular mechanisms by which the ligation of the T cell receptor to its ligand, an MHC-peptide complex, activates T cells. To this aim we have crystallized and solved the structure of two TCR/pMHC complexes. No conformational changes were evidenced in these complexes. We are trying now to reconstruct a larger TCR complex including CD3 dimers and CD4/CD8 molecules. Similar studies are carried out on TCR/pMHC pairs involved in autoimmune diseases with two additional goals. First, identify self-peptides involved in autoimmunity. Secondly, measure the affinity of self MHC-self pMHC complexes and determine if pathogenic T cells arise from escaping negative selection or breakage of peripheral tolerance. The corollary question is to determine if autoimmunity is a deviance of a normal immune response or the innate property of a T cell response against a self antigen. The answers to these questions will be determinant in choosing new therapeutic strategies.

Education

Ph.D., Immunology, University of Paris Diderot (Paris VII), 1987
M.D., Medicine, University of Caen Lower Normandy, 1980

Selected References

Garcia, K.C., L.Teyton, and I.A.Wilson 1999, Structural basis of immune recognition, Ann.Rev.Immunol., 17:369-397

Corper, A.L., Stratmann, T., Apostolopoulos, V., Scott, C.A., Garcia, K.C., Kang, A., Wilson, I.A., and Teyton, L. 2000. A structural framework for deciphering the link between I-A^g7 and murine autoimmune diabetes. Science. 288:505-511

Homann, D., Teyton, L., Oldstone, M.B. 2001. Differential regulation of antiviral T-cell immunity results in stable CD8+ but declining CD4+ T-cell memory. Nat Med. 7: 913-919

Benlagha, K., , Kyin, T., Beavis, A., Teyton, L., Bendelac, A. 2002. A thymic precursor to the NKT cell lineage. Science, 296: 553-555

Links

Ongoing Collaboration Between TSRI and Princeton Scientists Reveals Details of Natural Killer T Cells