Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI041580-03
Application #
6201374
Study Section
Project Start
1999-08-01
Project End
2000-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

van Deventer, Hendrik W; Serody, Jonathon S; McKinnon, Karen P et al. (2002) Transfection of macrophage inflammatory protein 1 alpha into B16 F10 melanoma cells inhibits growth of pulmonary metastases but not subcutaneous tumors. J Immunol 169:1634-9
June Brickey, W; Felix, Nathan J; Griffiths, Robert et al. (2002) Prolonged survival of class II transactivator-deficient cardiac allografts. Transplantation 74:1341-8
Felix, Nathan J; de Serres, Suzan; Meyer, Anthony A et al. (2002) Comparison of Abeta(b-/-), H2-DM(-), and CIITA(-/-) in second-set skin allograft rejection. J Surg Res 102:185-92
Tisch, R; Wang, B; Weaver, D J et al. (2001) Antigen-specific mediated suppression of beta cell autoimmunity by plasmid DNA vaccination. J Immunol 166:2122-32
Taxman, D J; Ting, J P (2001) Identification of novel Mycoplasma hyorhinis gene fragments by differential display analysis of co-cultures. J Microbiol Methods 44:217-23
Weaver Jr, D J; Liu, B; Tisch, R (2001) Plasmid DNAs encoding insulin and glutamic acid decarboxylase 65 have distinct effects on the progression of autoimmune diabetes in nonobese diabetic mice. J Immunol 167:586-92
Maile, R; Wang, B; Schooler, W et al. (2001) Antigen-specific modulation of an immune response by in vivo administration of soluble MHC class I tetramers. J Immunol 167:3708-14
Taxman, D J; Cressman, D E; Ting, J P (2000) Identification of class II transcriptional activator-induced genes by representational difference analysis: discoordinate regulation of the DN alpha/DO beta heterodimer. J Immunol 165:1410-6
Wang, B; Maile, R; Greenwood, R et al. (2000) Naive CD8+ T cells do not require costimulation for proliferation and differentiation into cytotoxic effector cells. J Immunol 164:1216-22
White 2nd, G C; Greenwood, R; Escobar, M et al. (2000) Hemophilia factor VIII therapy. Immunological tolerance. A clinical perspective. Haematologica 85:113-6

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