The long range goals of the research efforts are to define and understand in molecular terms the roles of the antigen receptor, antigen, the major histocompatibility complex (MHC) molecules, and other T and B cell surface molecules in the generation of an immune response. The goals of the current proposal are directed towards the investigation of the expression and functional significance of a mixed isotype class II MHC molecule initially identified on the surface of a murine B cell lymphoma.
The specific aims of the proposed research are: 1) to investigate the occurrence of mixed isotype class II molecules among normal [and autoimmune mouse strains] class II expressing cells using monoclonal antibody antibodies specific for the mixed isotype class II molecule, EaAb. These monoclonal antibodies have been recently produced by somatic cell hybridization of immune hamster spleen cells and a mouse myeloma fusion partner. The expression of the unusual class II antigen on resting and activated cell populations [and cells obtained at different stages of disease progression in autoimmune mouse stains] will be assayed by immunofluorescent [and immunohistological] staining techniques; 2) to study the biological function of the mixed isotype class II molecule. Can this molecule serve as a MHC restriction element for antigen-specific T cell responses and/or as an alloantigen?; 3) to determine the molecular basis for the expression of the mixed isotype class II molecule, EdaAdb, on the murine B cell lymphoma, 2PK3, using molecular biological techniques to analyze the class II MHC RNA and DNA products; 4) to analyze the class II MHC antigen expressed by another B cell lymphoma, the RCS-5 tumor of the SJL mouse for the possible expression of an AsaEsb mixed isotype class II MHC. The results of this investigation should make important contributions to the knowledge of the biology of the MHC. The expression of a mixed isotype class II MHC antigen on normal cells would indicate a greater potential to the polymorphisms class II MHC restriction elements and to alloantigenicity. This novel form of class II antigens may help to explain certain autoimmune and HLA-D disease associations, particularly those where multiple loci appear to be involved.
| Spencer, J S; Freed, J H; Kubo, R T (1993) Expression and function of mixed isotype MHC class II molecules in normal mice. J Immunol 151:6822-32 |
| Spencer, J S; McCormack, J E; Kubo, R T (1992) Characterization of defective I-A surface expression in a mixed isotype expressing murine B cell lymphoma: continued expression of E alpha d A beta d despite competition from restored A alpha d A beta d pairs. Int Immunol 4:905-15 |
| Pullen, A M; Bill, J; Kubo, R T et al. (1991) Analysis of the interaction site for the self superantigen Mls-1a on T cell receptor V beta. J Exp Med 173:1183-92 |
