Abstract

The focus of this proposal is to learn the fundamental structural characteristics of Ia antigens of the major histocompatibility complex of the mouse and to understand the molecular basis for immune responsiveness. The relationship between the expression of Ia molecules in F1 hybrids and immune responsiveness will be determined. New highly specific monoclonal antibody reagents will be used in this study. They will be generated by Doolittle's method, using protein sequence data which will be obtained by microsequencing large (CNBr) fragments of Ia polypeptides. These biochemical techniques will also be used to determine whether or not a non-polymorphic (invarient) polypeptide, which co-purifies with Ia, is an intergral part of a functioning Ia molecule. This basic approach should eventually lead to an understanding at a molecular level of the role which Ia antigens play in the control of the immune response. This is a prerequisite for the successful manipulation of the immune response and should result in rational molecular therapies for many varied diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
9R01GM036804-04
Application #
3291292
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1985-09-27
Project End
1986-08-31
Budget Start
1985-09-27
Budget End
1986-08-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033

  Publications

Ochoa-Garay, J; McKinney, D M; Kochounian, H H et al. (1997) The ability of peptides to induce cytotoxic T cells in vitro does not strongly correlate with their affinity for the H-2Ld molecule: implications for vaccine design and immunotherapy. Mol Immunol 34:273-81
Louie, K A; Ochoa-Garay, J; Chen, P J et al. (1996) H-2Ld-alloreactive T cell hybridomas utilize diverse V alpha and V beta T cell receptor chains. Mol Immunol 33:747-58
Frelinger, J A; McMillan, M (1996) The role of peptide specificity in MHC class I-restricted allogeneic responses. Immunol Rev 154:45-58
Killion, C C; Chen, P J; Dadgari, J M et al. (1995) Dissection of cross-reactivities using a panel of H-2Ld alloreactive T cell hybridomas. Cell Immunol 164:81-9
Benichou, G; Fedoseyeva, E; Lehmann, P V et al. (1994) Limited T cell response to donor MHC peptides during allograft rejection. Implications for selective immune therapy in transplantation. J Immunol 153:938-45
Benichou, G; Fedoseyeva, E; Olson, C A et al. (1994) Disruption of the determinant hierarchy on a self-MHC peptide: concomitant tolerance induction to the dominant determinant and priming to the cryptic self-determinant. Int Immunol 6:131-8
Fahnestock, M L; Dadgari, J M; McMillan, M et al. (1994) Phosphatidyl inositol-linked forms of a murine class I MHC molecule expressed on Chinese hamster ovary cells retain peptide binding capability and alloreactivity. Int Immunol 6:307-14
McKinney, D M; Chen, P; McMillan, M (1994) Single Dd amino acid substitutions in the H-2Ld molecule identify antibody epitopes. Immunogenetics 39:440-3
Hioe, C E; McKinney, D M; Frelinger, J A et al. (1994) Mutations inside but not outside the peptide binding cleft of the H-2 Ld molecule affect CTL recognition and binding of the nucleoprotein peptide from the lymphocytic choriomeningitis virus. Immunogenetics 40:222-9
Benichou, G; Takizawa, P A; Olson, C A et al. (1992) Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection. J Exp Med 175:305-8

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