Development of Improved Immunodiagnostics and Synthetic Vaccines
Immunology
Clemencia Pinilla, Ph.D.
Associate Member
Email:
Development of Improved Immunodiagnostics and Synthetic Vaccines
Our current research focuses on the study of T cell clones derived from the cerebrospinal fluid (CSF) of patients with multiple sclerosis. Since these clones are derived from the CSF they can be considered clinically relevant, and the antigens that they recognize are likely to be involved in the disease process. These studies are being carried out in collaboration with Dr. Roland Martin's group at the National Institute of Neurological Disorders and Stroke.
The identification of candidate autoantigens for these T cell clones will be carried out using the synthetic combinatorial libraries developed at the Institute. Our previous studies with clones of known specificity have shown that the use of combinatorial libraries provides information which corresponds to the known antigens.
Furthermore, these libraries can be used in combination with biometric algorithms for the identification of possible antigens through the search of protein databases. This approach has led to the identification of many peptides derived from Borrelia burgdorferi and molecular mimics from human proteins recognized by a T cell clone derived from the CSF of a patient with chronic Lyme disease. These efforts will have direct applications toward the development of improved immunodiagnostics and synthetic vaccines.
In addition, T cell clones specific for Copaxone®, which is a current treatment for MS, are being studied using synthetic combinatorial libraries to better understand the possible mechanism of action of Copaxone®. The results of these studies are expected to aid in the development of improved treatments.
Key References
1. Hemmer, B., Gran, B., Zhao, Y., Marques, A., Pascal, J., Tzou, A., Kondo, T., Cortese, I., Bielekova, B., Straus, S., McFarland, H. F., Houghten, R. A., Simon, R., Pinilla, C., and Martin, R. Identification of candidate T cell epitopes and molecular mimics in chronic Lyme Disease. Nature Medicine 5:1375-1382, 1999.
2. Markovic-Plese, C., Pinilla, C. and Martin, R. Molecular mimicry in multiple sclerosis: New insights from studying T cell receptor degeneracy. Immunol. News 6:185-186, 1999.
3. Pinilla, C., R. Martin, B. Gran, J. R. Appel, C. Boggiano, D. B. Wilson, and R. A. Houghten. Exploring immunological specificity using synthetic peptide combinatorial libraries. Curr. Opin. Immunol. 11:193-202, 1999.
4. Houghten, R. A., C. Pinilla, J. R. Appel, S. E. Blondelle, C. T. Dooley, J. Eichler, A. Nefzi, and J. M. Ostresh. Mixture-based synthetic combinatorial libraries. J. Med. Chem. 42:3743-3778, 1999.
5. Pinilla, C., J. R. Appel, G. D. Campbell, J. Buencamino, N. Benkirane, S. Muller, and N. Greenspan. All D-peptides recognized by an anti-carbohydrate antibody identified from a positional scanning library. J. Mol. Biol. 283:1013-1025, 1998.
6. Hemmer, B., M. Vergelli, C. Pinilla, R. Houghten, and R. Martin. Probing degeneracy in T-cell recognition using peptide combinatorial libraries. Immunol. Today 19:163-168, 1998.