Abstract

This application proposes studies in a variety of areas relating to the chemistry and biology of human lymphocytes. The problems being studied involve the molecular basis of immune recognition, including the recognition of tumor cells, as well as factors which govern and regulate proliferation of human lymphocytes. The techniques being employed include protein chemistry and crystallography, molecular genetics, cellular immunology and virology. Specific areas of investigation are: 1) protein chemistry and crystallography of and the relationship of structure to function in class I MHC molecules and their bound peptides, 2) similar studies of class II MHC molecules, 3) the interaction of CD4 with the class Il MHC molecule through its D3 and D4 domains and with the protein tyrosine kinase p56(lck) through its intracytoplasmic region, 5) protein chemistry of T cell receptors and the mechanisms of development of T cells, 6) the role of HLA-C in NK allorecognition and other studies of NK cells, 7) the mechanism of transformation of B and T cells by Epstein Barr Virus, and 8) the regulation of expression and function of tumor necrosis factor alpha. They relate to tumor immunology and tumor cell proliferation in a variety of ways.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
5R35CA047554-13
Application #
6328908
Study Section
Special Emphasis Panel (SRC (90))
Program Officer
Mccarthy, Susan A
Project Start
1988-09-30
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2002-11-30
Support Year
13
Fiscal Year
2001
Total Cost
$2,185,830
Indirect Cost

  Institution

Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138

  Publications

Nieuwenhuis, Edward E S; Gillessen, Silke; Scheper, Rik J et al. (2005) CD1d and CD1d-restricted iNKT-cells play a pivotal role in contact hypersensitivity. Exp Dermatol 14:250-8
Deng, Lih-Wen; Chiu, Isaac; Strominger, Jack L (2004) MLL 5 protein forms intranuclear foci, and overexpression inhibits cell cycle progression. Proc Natl Acad Sci U S A 101:757-62
Wong, Siew Heng; Santambrogio, Laura; Strominger, Jack L (2004) Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins. Proc Natl Acad Sci U S A 101:17783-8
Koopman, Louise A; Kopcow, Hernan D; Rybalov, Basya et al. (2003) Human decidual natural killer cells are a unique NK cell subset with immunomodulatory potential. J Exp Med 198:1201-12
Potolicchio, Ilaria; Santambrogio, Laura; Strominger, Jack L (2003) Molecular interaction and enzymatic activity of macrophage migration inhibitory factor with immunorelevant peptides. J Biol Chem 278:30889-95
Re, Fabio; Strominger, Jack L (2002) Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness. J Biol Chem 277:23427-32
Re, Fabio; Belyanskaya, Svetlana L; Riese, Richiard J et al. (2002) Granulocyte-macrophage colony-stimulating factor induces an expression program in neonatal microglia that primes them for antigen presentation. J Immunol 169:2264-73
Malik, Pratap; Klimovitsky, Polina; Deng, Lih-Wen et al. (2002) Uniquely conformed peptide-containing beta 2-microglobulin-free heavy chains of HLA-B2705 on the cell surface. J Immunol 169:4379-87
Boyson, Jonathan E; Erskine, Robert; Whitman, Mary C et al. (2002) Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci U S A 99:16180-5
Rotzschke, Olaf; Lau, Julie M; Hofstatter, Maria et al. (2002) A pH-sensitive histidine residue as control element for ligand release from HLA-DR molecules. Proc Natl Acad Sci U S A 99:16946-50

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