The applicants propose a project to investigate the biological and biochemical consequences of mice expressing a single peptide covalently tethered to a class I MHC molecule. The investigators will construct transgenic mice which express this molecule and investigate its effect on T cell selection in both B6 mice that have the normal array of T cell receptors (TCR) and mice transgenic for the TCR specific for the covalently attached peptide/class I complex. The applicants will investigate the biological effects of exposure to a homogeneous class I molecule and its ability to produce deletion and/or anergy in vitro and in skin grafts from congenic LCMV GP transgenic mice. The investigators will also investigate the biochemistry of these molecules by examining their peptide binding capabilities and thermostability to define their potential as therapeutic agents. The applicants will determine the crystal structure of D(b) linked to the LCMV GP peptide KAVYNFATM and compare them to the wild type molecules to physically examine the consequences of this type of linkage. Finally, the applicants will use soluble, tethered molecules as therapeutics to alter both peptide specific and allogenic response.

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University of North Carolina Chapel Hill
Chapel Hill
United States
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