Recent studies of H-2L, a second D region gene in the murine major histocompatibility complex (H-2), have intensified our interest in pursuing research on the heterogeneity of H-2D region genes and gene products. These new findings include: 1) H-2L antigens have been found to display several unique properties which distinguish them from H-2K and D antigens; 2) molecular heterogeneity in addition to D and L has been reported in studies of certain D regions, whereas other D regions appear to determine a single gene product; 3) two putative H-2L genes have been independently cloned, each having a unique DNA sequence; and 4) a dominant idiotype has been found in the humoral response to Ld antigens. In the proposed study, we will extend our knowledge of H-2 antigens by exploiting knowledge already gained from the study of H-2L antigens. New alloantisera and monoclonal antibodies to D region-encoded antigens will be produced using mouse strain combinations such that only select determinants are recognized. To probe the B-cell recognition of D region encoded antigens, the idiotypes of these reagents will be compared using anti-idiotypic reagents produced to monoclonal antibodies. Precipitates formed with anti-H-2D reagents will be chemically compared by sequential precipitation, 2-D gels, peptide maps, and amino acid sequence analyses. Furthermore, these reagents will be used to: 1) explore the linkage relationship of D region loci; 2) quantitate the cell surface expression of D region loci; 2) quantitate the cell surface expression of D region-associated gene products; and 3) probe the T-cell recognition of specific D region determinants in allogeneic and virus-specific cytotoxic responses. Recognition of H-2 antigens by T-cells will also be investigated using cloned T-cell lines and T-cell hybridomas which recognize, or are restricted by, D region antigens. These homogeneous cell lines in conjunction with the above described reagents will be used to probe the role of idiotype in the T cell recognition of H-2 antigens. The information acquired in this study will help elucidate the genetics, evolution and structure of major histocompatibility antigens as well as probe the immunologic mechanisms of MHC restriction and T-cell cytotoxicity.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Immunobiology Study Section (IMB)
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Washington University
Schools of Medicine
Saint Louis
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Ghasemi, Reza; Lazear, Eric; Wang, Xiaoli et al. (2016) Selective targeting of IL-2 to NKG2D bearing cells for improved immunotherapy. Nat Commun 7:12878
Lubman, Olga Y; Fremont, Daved H (2016) Parallel Evolution of Chemokine Binding by Structurally Related Herpesvirus Decoy Receptors. Structure 24:57-69
Nelson, Christopher A; Epperson, Megan L; Singh, Sukrit et al. (2015) Structural Conservation and Functional Diversity of the Poxvirus Immune Evasion (PIE) Domain Superfamily. Viruses 7:4878-98
Kim, Sojung; Pinto, Amelia K; Myers, Nancy B et al. (2014) A novel T-cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice. Eur J Immunol 44:1936-46
Lubman, Olga Y; Cella, Marina; Wang, Xinxin et al. (2014) Rodent herpesvirus Peru encodes a secreted chemokine decoy receptor. J Virol 88:538-46
McCoy 4th, William H; Wang, Xiaoli; Yokoyama, Wayne M et al. (2013) Cowpox virus employs a two-pronged strategy to outflank MHCI antigen presentation. Mol Immunol 55:156-8
Wang, Xiaoli; Yu, Y Y Lawrence; Myers, Nancy et al. (2013) Decoupling the role of ubiquitination for the dislocation versus degradation of major histocompatibility complex (MHC) class I proteins during endoplasmic reticulum-associated degradation (ERAD). J Biol Chem 288:23295-306
Mage, Michael G; Dolan, Michael A; Wang, Rui et al. (2013) A structural and molecular dynamics approach to understanding the peptide-receptive transition state of MHC-I molecules. Mol Immunol 55:123-5
Lazear, Eric; Peterson, Lance W; Nelson, Chris A et al. (2013) Crystal structure of the cowpox virus-encoded NKG2D ligand OMCP. J Virol 87:840-50
Mage, Michael G; Dolan, Michael A; Wang, Rui et al. (2012) The peptide-receptive transition state of MHC class I molecules: insight from structure and molecular dynamics. J Immunol 189:1391-9

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