Abstract

A great deal has been learned about the structure and function of human histocompatibility antigens in the past thirty years. Some details remain to be elucidated but, in addition, the information already obtained can be used to explore the relationship of these proteins to human diseases.
The specific aims of this application are: 1. To develop murine models of pemphigus vulgaris employing human genes and to use these models to identify disease-related peptide epitopes bound to human Class 11 MHC proteins. 2. To examine the relationship between HLA-DP (a Class II MHC protein) and Hard Metal Diseases. 3. To examine the basis of the reactivity of a subset of HLA-B27 molecules (a class I MHC protein linked to ankylosing spondylitis) with an unusual monoclonal antibody MARB-4 and whether this subset might be related to the disease. 4. To examine the basis for the effectiveness of Copolymer 1 in the treatment of multiple sclerosis [genetically linked to the Class II MHC protein HLA-DR2 (DRB1*1501)] and to examine the possibility that more effective copolymers could be designed for the therapy of this disease, as well as for the therapy of the autoimmune disease (i.e. rheumatoid arthritis). 5. To utilize oligomerized T cell epitopes to study mouse models of, multiple sclerosis and pemphigus vulgaris, both of which are linked to specific alleles of Class II MHC genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049524-02
Application #
6511363
Study Section
Immunological Sciences Study Section (IMS)
Program Officer
Esch, Thomas R
Project Start
2001-09-01
Project End
2006-05-31
Budget Start
2002-07-01
Budget End
2003-05-31
Support Year
2
Fiscal Year
2002
Total Cost
$767,582
Indirect Cost

  Institution

Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

Koenig, Paul-Albert; Spooner, Eric; Kawamoto, Norio et al. (2013) Amino acid copolymers that alleviate experimental autoimmune encephalomyelitis in vivo interact with heparan sulfates and glycoprotein 96 in APCs. J Immunol 191:208-16
Kawamoto, Norio; Ohnishi, Hidenori; Kondo, Naomi et al. (2013) The role of dendritic cells in the generation of CD4(+) CD25(HI) Foxp3(+) T cells induced by amino acid copolymers. Int Immunol 25:53-65
Kovalchin, Joseph; Krieger, Jeffrey; Genova, Michelle et al. (2011) Macrophage-specific chemokines induced via innate immunity by amino acid copolymers and their role in EAE. PLoS One 6:e26274
Kato, Zenichiro; Stern, Joel N H; Nakamura, Hironori K et al. (2010) The autoimmune TCR-Ob.2F3 can bind to MBP85-99/HLA-DR2 having an unconventional mode as in TCR-Ob.1A12. Mol Immunol 48:314-20
Strominger, Jack L (2010) An alternative path for antigen presentation: group 1 CD1 proteins. J Immunol 184:3303-5
Stern, Joel N H; Keskin, Derin B; Kato, Zenichiro et al. (2010) Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells. Proc Natl Acad Sci U S A 107:17280-5
Yin, Hongen; Vistica, Barbara P; Chan, Chi-Chao et al. (2009) Inhibition of experimental autoimmune uveitis by amino acid copolymers. J Neuroimmunol 215:43-8
Zhang, Hong; Stern, Joel N H; Strominger, Jack L (2009) T cell receptors in an IL-10-secreting amino acid copolymer-specific regulatory T cell line that mediates bystander immunosuppression. Proc Natl Acad Sci U S A 106:3336-41
Stern, Joel N H; Keskin, Derin B; Zhang, Hong et al. (2008) Amino acid copolymer-specific IL-10-secreting regulatory T cells that ameliorate autoimmune diseases in mice. Proc Natl Acad Sci U S A 105:5172-6
Krzewski, Konrad; Chen, Xi; Strominger, Jack L (2008) WIP is essential for lytic granule polarization and NK cell cytotoxicity. Proc Natl Acad Sci U S A 105:2568-73

Showing the most recent 10 out of 26 publications