We have described an experimental model in which variant peptides are introduced in fetal thymic organ culture to determine whether they have the ability to promote differentiation of T cells of a defined specificity. Identification of a family of such peptides opens the possibility of directly addressing the relationship between MHC- associated peptides that select a mature T cell in the thymus and the particular foreign peptide that induces activation of this same T cell in the periphery. One widely discussed model suggests that reduced affinity of interaction between T cell receptor and an MHC:self-peptide complex could result in positive rather than negative selection in the thymus. In collaboration with David Margulies (Laboratory of Immunology, NIAID, NIH), we will exploit recent advances in the ability to engineer T cell receptor cDNA to facilitate isolation of soluble receptor molecules. We will then determine the relative affinity and kinetics of binding of purified TCR for complexes of soluble H-2Kb with either unmodified ligands or with the structurally related peptide analogs that were employed to positively select mature T cells that express this TCR.
| Zauderer, M; Singer, A (1997) Limiting dilution analysis of primary cytotoxic T-cell precursors. J Immunol Methods 208:85-90 |
| Merchlinsky, M; Eckert, D; Smith, E et al. (1997) Construction and characterization of vaccinia direct ligation vectors. Virology 238:444-51 |
| Westbay, T D; Dascher, C C; Hsia, R C et al. (1995) Deviation of immune response to Chlamydia psittaci outer membrane protein in lipopolysaccharide-hyporesponsive mice. Infect Immun 63:1391-3 |
| Westbay, T D; Dascher, C C; Hsia, R C et al. (1994) Dissociation of immune determinants of outer membrane proteins of Chlamydia psittaci strain guinea pig inclusion conjunctivitis. Infect Immun 62:5614-23 |
| Burstyn, D; Zauderer, M (1989) Requirements for stimulation of autoreactive T cells by thymic stroma. J Immunol 143:1422-5 |
