The immune system is remarkably efficient in discriminating self from nonself and is equipped with an array of effector mechanisms designed to destroy foreign entities. However, in certain pathological conditions, the immune system mistakenly recognizes a self component as if it were foreign and initiates a destructive immune response against this self component. These pathological conditions, known as autoimmune diseases, account for a wide array of human diseases including arthritis, diabetes, myasthenia gravis, and multiple sclerosis among many others. Our research is focused upon the molecular and cellular basis of an autoimmune disease known as experimental autoimmune encephalitis (EAE). In this disease, experimental animals experience a paralytic autoimmune attack against the myelin sheath of central nervous system axons. Due to the clinical and histological features of this disease, EAE is widely regarded as a relevant animal model for human demyelinating diseases such as multiple sclerosis. Our primary research interest involves characterizing the immunological pathway responsible for EAE in Lewis rats. This immunological pathway is comprised of accessory cells that "process" myelin specific determinants and "present" these determinants to activate EAE-inducing T helper lymphocytes. Specifically, our research is directed toward identifying the molecular messengers that mediate communication between accessory cells and myelin specific T helper lymphocytes. That is, we study the antigenic determinants, adhesion molecules, and interleukins required for the activation of encephalitogenic T cells as measured by EAE adoptive transfer activity, lymphokine production, and cellular proliferation. We also utilize B and T cell hybridoma technology together with techniques of protein chemistry and molecular biology to identify pivotal mediators of autoimmunity.

Arnold, P. Y. and M. D. Mannie. 1999. Vesicles bearing MHC class II molecules mediate transfer of antigen from antigen presenting cells to CD4+ T cells. Eur. J. Immunol. 29, 1363-1373.

Mannie, M. D. 1999. Immunological self/ nonself discrimination: integration of self versus nonself during cognate T cell interactions with antigen presenting cells. Immunol. Res. 19, 65-87.

Patel, D. M., P. Y. Arnold, G. A. White, J. P. Nardella, and M. D. Mannie. 1999. Class II MHC/ peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J. Immunol. 163, 5201-5210.

Walker, M. R., G. A. White, J. P. Nardella, and M. D. Mannie. 1999. An autologous self antigen differentially regulates expression of I-A glycoproteins and B7 costimulatory molecules on CD4-CD8- T-helper cells. J. Leuk. Biol. 66, 120-126.

Walker, M. R. and M. D. Mannie. 2001. T cell recognition of rat myelin basic protein as a TCR antagonist inhibits reciprocal activation of APC and engenders resistance to experimental autoimmune encephalomyelitis. Eur. J. Immunol. 31, 1894-1899.

Mannie, M. D. and M. W. Walker. 2001. Feedback activation of T cell antigen presenting cells during antigen-specific interactions with T cell responders. J. Leuk. Biol. 70, 252-260.

Mannie, M. D. 2001. T cell-mediated antigen presentation: a potential mechanism of infectious tolerance. Immunol. Res. 23, 1-21.

Norris, M. S., T. J. McConnell, and M. D. Mannie. 2001. Interleukin-2 promotes antigenic reactivity of rested T cells but prolongs the post-activational refractory phase of activated T cells. Cell. Immunol. 211, 51-60.

Mannie, M. D and M. S. Norris. 2001. MHC class II-restricted antigen presentation by myelin basic protein-specific CD4+ T cells causes prolonged desensitization and outgrowth of CD4- responders. 212, 51-62.

Patel, D. M., R. W. Dudek, and M. D. Mannie. 2001. Intercellular exchange of class II MHC complexes: ultrastructural localization and functional presentation of adsorbed I-A peptide complexes. Cell. Immunol. 214, 21-34.

Patel, D. M. and M. D. Mannie. 2001. Intercellular exchange of class II MHC/ peptide complexes is a conserved process that requires activation of T cells but is constitutive in other types of APC. Cell. Immunol. 214, 165-172.

Walker, M. R. and M. D. Mannie. 2002. Acquisition of functional MHC class II/ peptide complexes by T cells during thymic development and CNS-directed pathogenesis. Cell. Immunol. 218, 13-25.

Mannie, M. D., D. J. Frasier, and T. J. McConnell. 2003. IL-4 responsive CD4+ T cells specific for myelin basic protein: IL-2 confers a prolonged postactivation refractory phase. Immunol Cell Biol. 81, 8-19.