The presence of anti-snRNP autoantibodies are often found in SLE patients. In these patients, antibodies to multiple components of this complex are detected. During the current grant period, the role of B cells in the origination of this immune response in mice in the context of molecular mimicry has been examined and preliminary data have been obtained indicating that accessory molecules which are involved in T-B cognate interactions may be important in the generation of an autoimmune response. This proposal is to extend the current work to examine how autoimmunity to the snRNP complex is originated and to identify important intercellular interactions that occur during the evolution of SLE.
Four specific aims are proposed: 1) to generate anti-snRNP immunoglobulin mice and to examine antigen processing of the snRNP by antigen specific APCs; 2) to study the ability of antigen specific APCs to prime autoreactive T cells and to determine how these T cells drive the spectrum of anti-snRNP autoantibody response; 3) to determine the role of accessory molecules in the anti-snRNP autoimmunity in normal and autoimmune prone MRL lpr/lpr and MRL +/+; and 4) to examine the interactions of autoimmune prone (MRL-derived) B and T cells with the repertoire of lymphocytes in non-autoimmune mice.
| Vudattu, Nalini K; Waldron-Lynch, Frank; Truman, Lucy A et al. (2014) Humanized mice as a model for aberrant responses in human T cell immunotherapy. J Immunol 193:587-96 |
| Harvey, Bohdan P; Raycroft, Maurice T; Quan, Timothy E et al. (2014) Transfer of antigen from human B cells to dendritic cells. Mol Immunol 58:56-65 |
| Mamula, Mark J (2014) Editorial: B cells: not just making immunoglobulin anymore. Arthritis Rheumatol 66:2-5 |
| Doyle, Hester A; Yang, Mei-Ling; Raycroft, Maurice T et al. (2014) Autoantigens: novel forms and presentation to the immune system. Autoimmunity 47:220-33 |
| Yang, Mei-Ling; Gee, Alaric J P; Gee, Renelle J et al. (2013) Lupus autoimmunity altered by cellular methylation metabolism. Autoimmunity 46:21-31 |
| Doyle, Hester A; Aswad, Dana W; Mamula, Mark J (2013) Autoimmunity to isomerized histone H2B in systemic lupus erythematosus. Autoimmunity 46:6-13 |
| Doyle, Hester A; Mamula, Mark J (2012) Autoantigenesis: the evolution of protein modifications in autoimmune disease. Curr Opin Immunol 24:112-8 |
| Raycroft, Maurice T; Harvey, Bohdan P; Bruck, Matthew J et al. (2012) Inhibition of antigen trafficking through scavenger receptor A. J Biol Chem 287:5310-6 |
| Harvey, Bohdan P; Quan, Timothy E; Rudenga, Benjamin J et al. (2008) Editing antigen presentation: antigen transfer between human B lymphocytes and macrophages mediated by class A scavenger receptors. J Immunol 181:4043-51 |
