We plan to study the biology of class I genes encoded by the major histocompatibility complex (MHC) of the inbred Balb/c mouse. We have previously cloned and mapped 36 class I genes falling into two categories-three classical transplantation genes which encode the restriction elements for cytotoxic T cells and 33 class I-like genes whose functions are unknown. We plan three major categories of experiments. (1) To express a foreign transplantation antigen (alloantigens) in nonimmunological tissues (pancreas and liver) and in selected iummune-related cells (B cell, T cell and macrophage-like cells). These studies should provide insights into mechanisms of immunological tolerance and H-2 restriction. (2) To secrete and purify large quantities of soluble transplantation antigens in order to crystallize these proteins and determine their three-dimensional structures by X-ray analysis. We will examine in this regard a series of Kb mutant molecules and eventually a transplantation antigen interacting with a peptide fragment. These studies should provide insights into the molecular interactions between H-2 molecules, T-cell receptors and antigen. (3) We have DNA probes specific for most of the class I genes. We plan to study the expression of the 36 class I genes in immunological tissues and cells, in selected nonimmunological tissues and in differentiating T and B cells and in activated T cells. These studies should provide useful lineage and differentiation markers for immune-related cell lines and may provide insights into the function of the class I-like molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI019624-09
Application #
3128962
Study Section
Immunobiology Study Section (IMB)
Project Start
1983-01-01
Project End
1992-12-31
Budget Start
1991-01-01
Budget End
1991-12-31
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
Name
California Institute of Technology
Department
Type
Schools of Arts and Sciences
DUNS #
078731668
City
Pasadena
State
CA
Country
United States
Zip Code
91125
Renthal, Nora E; Guidry, Paula A; Shanmuganad, Sharmila et al. (2011) Isoforms of the nonclassical class I MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide. Immunogenetics 63:57-64
Swanson 2nd, Phillip A; Pack, Christopher D; Hadley, Annette et al. (2008) An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. J Exp Med 205:1647-57
Chiang, Eugene Y; Stroynowski, Iwona (2006) The role of structurally conserved class I MHC in tumor rejection: contribution of the Q8 locus. J Immunol 177:2123-30
Chen, Ming; Tabaczewski, Piotr; Truscott, Steven M et al. (2005) Hepatocytes express abundant surface class I MHC and efficiently use transporter associated with antigen processing, tapasin, and low molecular weight polypeptide proteasome subunit components of antigen processing and presentation pathway. J Immunol 175:1047-55
Chiang, Eugene Y; Stroynowski, Iwona (2005) Protective immunity against disparate tumors is mediated by a nonpolymorphic MHC class I molecule. J Immunol 174:5367-74
Chiang, Eugene Y; Stroynowski, Iwona (2004) A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor. J Immunol 173:4394-401
Chiang, Eugene Y; Henson, Maile; Stroynowski, Iwona (2003) Correction of defects responsible for impaired Qa-2 class Ib MHC expression on melanoma cells protects mice from tumor growth. J Immunol 170:4515-23
Gao, Jian-Xin; Liu, Xingluo; Wen, Jing et al. (2003) Two-signal requirement for activation and effector function of natural killer cell response to allogeneic tumor cells. Blood 102:4456-63
Chiang, Eugene Y; Henson, Maile; Stroynowski, Iwona (2002) The nonclassical major histocompatibility complex molecule Qa-2 protects tumor cells from NK cell- and lymphokine-activated killer cell-mediated cytolysis. J Immunol 168:2200-11
He, X; Tabaczewski, P; Ho, J et al. (2001) Promiscuous antigen presentation by the nonclassical MHC Ib Qa-2 is enabled by a shallow, hydrophobic groove and self-stabilized peptide conformation. Structure 9:1213-24

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