Previous studies supported by this grant have provided a clear picture of the expression of Ia glycoprotein antigens on the lymphocyte surface. In addition, we have shown that Ia antigens are the molecular products of immune response (Ir) genes, and that quantitative as well as qualitative (allelic) differences in Ia expression influence immune response potential. The goals of the current proposal are to 1) determine the extent, nature, and functional relevance of quantitative and qualitative microheterogeneity in the expression of Ia molecules on the cell surface, which has only been peripherally explored, and 2) determine whether suppression universally accounts for nonresponsiveness in Ir nonresponder mice, and explore possible mechanisms of this nonresponsiveness (e.g. self tolerance). To achieve these goals, we will utilize conventional Ia antisera and monoclonal Ia antibodies, two dimensional gel electrophoresis, and T cells and cloned autoreactive T cell lines to probe the genetics, expression, and biology of Ir products. In addition, we will apply two novel systems which we have developed to the analysis of the role of immune suppression in self tolerance and Ir gene function (contrasuppression and stimulation in I-J disparate strains). The long term objective of this research is to determine the contribution of quantitative and qualitative microheterogeneity in Ia expression to immune response capacity, and to determine the precise mechanism(s) of Ir gene control.
| Lee, W T; Shiledar-Baxi, V; Winslow, G M et al. (1998) Self-restricted dual receptor memory T cells. J Immunol 161:4513-9 |
| Makino, M; Murphy, D B; Melvold, R W et al. (1995) Impact of MHC class I gene on resistance to murine AIDS. Scand J Immunol 42:368-72 |
| Makino, M; Tang, Y; Murphy, D B et al. (1994) Influence of H-2 class II antigens on the development of murine AIDS. J Immunol 152:4157-64 |
| Bryda, E C; DePari, J A; Sant'Angelo, D B et al. (1992) Multiple sites of crossing over within the Eb recombinational hotspot in the mouse. Mamm Genome 2:123-9 |
| Murphy, D B; Rath, S; Pizzo, E et al. (1992) Monoclonal antibody detection of a major self peptide. MHC class II complex. J Immunol 148:3483-91 |
| Van Kaer, L; Wu, M; Ichikawa, Y et al. (1991) Recognition of MHC TL gene products by gamma delta T cells. Immunol Rev 120:89-115 |
| Ito, K; Van Kaer, L; Bonneville, M et al. (1990) Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell 62:549-61 |
| Homer, R J; Murphy, D B (1987) Qc-1, a novel Q-region-controlled CTL determinant expressed on B lymphocytes. J Immunol 138:4322-8 |
| Flood, P M; Benoist, C; Mathis, D et al. (1986) Altered I-J phenotype in E alpha transgenic mice. Proc Natl Acad Sci U S A 83:8308-12 |
| Philipps, C; McMillan, M; Flood, P M et al. (1985) Identification of a unique tumor-specific antigen as a novel class I major histocompatibility molecule. Proc Natl Acad Sci U S A 82:5140-4 |
