Abstract

Studies on the structure-function analysis of murine Ia molecules will be done utilizing Ia molecules altered by site-directed in vitro mutagenesis. Murine AK alpha or AK beta molecules will be altered by substituting the d allele specific residues at each of the polymorphic positions within the alpha-1 or beta-1 domains. Substitutions will be made one residue at a time or entire allelically variable regions will be changed such that the alpha- 1 or beta-I domains are more like the d allele sequence. The altered genes will be transfected into M12.C3 cells or L cells by electroporation and the cells tested for loss and gain alterations in k or d allele specific serologic epitopes or antigen presentation function to T cell hybrids. These mutants will also be utilized to identify regions on the Ia molecule that are important for alpha/beta chain pairing and for intracellular transport.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026297-11
Application #
3167243
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1980-01-01
Project End
1992-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
11
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905

  Publications

Wade, W F; Khrebtukova, I; Schreiber, K L et al. (1995) Truncated MHC class II cytoplasmic and transmembrane domains: effect on plasma membrane expression. Mol Immunol 32:433-46
Wei, B Y; Schreiber, K; Buerstedde, J M et al. (1994) Substitution of class II alpha chain polymorphic residues defines location of A alpha k serologic epitopes and alters association between alpha beta and Ii polypeptides. Int Immunol 6:297-305
Schreiber, K L; Bell, M P; Huntoon, C J et al. (1994) Class II histocompatibility molecules associate with calnexin during assembly in the endoplasmic reticulum. Int Immunol 6:101-11
Beck, B N; Nilson, A E; Bell, M P et al. (1991) The contribution of beta-strand residues to serologic epitopes on the A beta k polypeptide. Immunogenetics 33:409-12
Wei, B Y; Buerstedde, J M; Bell, M et al. (1991) Functional effects of N-linked oligosaccharides located on the external domain of murine class II molecules. J Immunol 146:2358-66
Lee, J M; McKean, D J; Watts, T H (1991) Functional mapping of MHC class II polymorphic residues. The alpha-chain controls the specificity for binding an Ad-versus an A k-restricted peptide and the beta-chain region 65-67 controls T cell recognition but not peptide binding. J Immunol 146:2952-9
Esch, T R; McKean, D J; Thomas, D W (1990) The role of Ia in the formation of a T cell antigen-recognition complex. J Immunol 145:3979-84
Beck, B N; McKean, D J (1990) Mapping T cell receptor epitopes on the A beta polypeptide. Immunol Res 9:47-56
Rosloniec, E F; Vitez, L J; Beck, B N et al. (1989) I-Ak polymorphisms define a functionally dominant region for the presentation of hen egg lysozyme peptides. J Immunol 143:50-8
Esch, T R; McKean, D J; Thomas, D W (1989) Identification of I-A beta-chain residues critical for T cell recognition of peptide antigens. Cell Immunol 123:226-35

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