Associate Professor
Ph.D. University of Oklahoma Health Science Center, 1994
The question of how autoimmunity is initiated and maintained has been argued for a considerable time; however, there is a consensus opinion that autoimmune disease is the product of several interacting factors, with genetics and environment contributing the greatest impact. Whether there is an environmental instigator which induces a lymphocyte response cross-reactive with a self-molecule ("molecular mimicry"), or whether the prime mover relates mainly to an inflammatory injury resulting from a microbial infection are critical to our understanding of the pathogenesis of autoimmune disease. For example, acute rheumatic fever, which represents one of the best examples of molecular mimicry, is an autoimmune disease that is preceded by a pharyngeal infection with group A streptococcus. Strikingly, molecules associated with streptococcus can mimic cardiac proteins and induce heart-reactive antibodies and T cells which are detected in the blood and hearts of patients with rheumatic heart disease. Nevertheless, the progression from infection to autoimmunity to autoimmune disease is a rare event such that the majority of individuals exposed to group A streptococcus - including those that may develop autoreactive antibodies - do not develop rheumatic heart disease. The evidence to date suggests that autoimmune responses in certain susceptible individuals will sufficiently perturb immunological homeostasis as to create a state of dysregulation and autoimmune disease. Our lab focuses on delineating the mechanisms that are involved in the activation and uncontrolled expansion of pathogenic autoimmune responses by microbial organisms. Conversely we are also engaged in studies to reveal the regulatory responses that seem to provide protection to normal individuals.
One of the most interesting animal models of autoimmune disease is insulin-dependent diabetes mellitus (IDDM) in the non-obese diabetic (NOD) mouse. IDDM in the NOD mouse results from a T lymphocyte-mediated destruction of the insulin-producing b cells of the pancreas and serves as a model for human type I diabetes. Prior to the onset of diabetes, young NOD mice develop T cell responses to the islet antigens glutamic acid decarboxylase (GAD65) and insulin. GAD65 and insulin; 1) are targets for autoreactive antibodies and T lymphocytes in young pre-diabetic NOD mice and humans (these responses are used for clinical diagnosis), 2) are capable of inducing diabetogenic T lymphocytes and overt diabetes, and 3) are the current focus of therapeutic approaches to prevent type I diabetes in humans. By studying T lymphocyte responses to GAD65 and insulin we hope to identify immunoregulatory mechanisms that can be used to induce specific regulation in both the CD4+ and CD8+ T lymphocyte compartments of the anti-islet response. We are currently investigating the activities of certain peptides that can alter the effector function of pathogenic GAD65-specfic T lymphocytes. Furthermore, are continuing our efforts to design and characterize peptides that can be used to induce the expansion of regulatory/protective T lymphocytes. The combination of these approaches should allow us to define fragments of self-molecules that can be used alone or in combination, to modulate the autoimmune response responsible for islet cell damage and IDDM in NOD mice. Moreover, the principles learned may provide important clues for the amelioration of T lymphocyte-mediated autoimmune diseases, such as diabetes, myocarditis, arthritis, and multiple sclerosis, in human as well.
Mayo, SM and A Quinn. Altered Susceptibility to EAE in Congenic NOD Mice: Altered Processing of the Encephalitogenic MOG35-55 Peptide by NOR/LtJ Mice.
In Press at Clinical Immunology
Busick, R, C. Aguilera, and A. Quinn. Dominant CTL Inducing Epitopes on GAD65 are Adjacent to or Overlap Dominant Th-Inducing Epitopes In NOD Mice. In Press Clinical immunology
Mayo, SM, W. Kohler, V. Kumar, and A. Quinn. 2006. Insulin-Dependent Diabetes Loci Idd5 and Idd9 Increase Sensitivity to Experimental Autoimmune Encephalomyelitis. Clinical Immunology 118:219-228.
A. Quinn, M. McInerney, D. Huffman, B. McInerney, S. Mayo, K. Haskins, and E. Sercarz. 2006. T Cells To A Dominant Epitope On GAD65 Express A Public CDR3 Motif. International Immunol 18:967-79.
Im, J, S, A. Quinn, E.E. Sercarz, and D.F. Lake. Molecular profile of the T Cell receptors of regulatory and effector CD4+ T cells recognizing overlapping determinants on glutamic acid decarboxylase (524-543). Molecular Immunology 40:971-980.
Nepom, G., A. Quinn, E. Sercarz, and D.B. Wilson. 2003. How important is GAD in the etiology of spontaneous disease in human and murine type 1 diabetes? J. Autoimmunity. 20:193-194
Quinn, A. Antigen-induced TID in NOD mice. 2003. Antigen-induced T1D in NOD mice. J. Autoimmunity. 20:207-210.
Melo, M.F., C.R. Gabaglia, K.D. Moudgil, E.E. Sercarz, and A. Quinn. 2002. Strain-dependent effect of nasal instillation of antigen on the immune response in mice. Israeli Medical Association Journal. 4(11 Supple):902-7.
Galvin, J.E., M.E. Herric, S.D. Kosanke, S.M. Factor, A. Quinn, and M.W. Cunningham. 2002. Induction of myocarditis and valvulitis in Lewis rats by different epitopes of cardiac myosin and its implications in rheumatic carditis. Am. J. Pathol. 160:297-306.
Quinn, A., V. Kumar, K.P. Jensen, and E.E. Sercarz. 2001. Interactions of effectors and regulators are decisive in the manifestations of type 1 diabetes in non-obese diabetic mice. Curr. Dir. Autoimmun. 4:171-92.
Quinn, A., M. McInereny, and E.E. Sercarz. 2001. MHC Class I-restricted determinants on the glutamic acid decarboxylase-65 molecule induce spontaneous CTL activity. J. Immunol. 167:1748-57.
Quinn, A., M.F. Melo, and E.E. Sercarz. 2001. Relative resistance to nasally-induced tolerance in non-obese diabetic mice but not other I-Ag7-expressing mouse strains. International Immunology 13:1321-33.
Kaufman, D.L., R. Tisch, N. Sarvetnick, L. Chatenoud, L.C. Harrison, K. Haskins, A. Quinn, E. Sercarz, B. Singh, M. von Herrath, D. Wegmann, L. Wen, and D. Zekzer. 2001. Report from the 1st International NOD Mouse T-Cell Workshop and the follow-up mini-workshop. Diabetes 50:2459-63.
Quinn, A., V. Kumar, K.P. Jensen, and E.E. Sercarz. 2001. Interactions of Effectors and Regulators are Decisive in the Manifestations of IDDM in NOD Mice in Molecular Pathology of Insulin-Dependent Diabetes Mellitus. M. von Herrath (Ed.), Basel, Karger.
Quinn, A., S. Kosanke, V.A. Fischetti, S.M. Factor, and M.W. Cunningham. 2001. Induction of autoimmune valvular heart disease by recombinant streptococcal M protein. Infection and Immunity 69:4072-80.
Quinn, A., , B. McInerney, O. Kim, E. Reich, K. Jensen, and E.E. Sercarz. 2001. Regulatory and effector CD4 T cells in NOD mice recognize overlapping determinants on GAD65 and use distinct Vβ genes. J. Immunol. 166:2982-2991.
Quinn, A. and E.E. Sercarz. 2000. Molecular Mimicry and Determinant Spreading in Molecular Mimicry, Microbes, and Autoimmunity. M.W. Cunningham and R.S. Fujinami (Ed.), Washington, DC: ASM Press.
Maverakis, E., J.T. Beech, S. Wilson, A. Quinn, B. Peterson, and E.E. Sercarz. 2000 T cell receptor CDR3-length analysis reveals the absence of a characteristic public T cell repertoire in neonatal tolerance: the response in the “tolerant” mouse within the residual repertoire is quantitatively similar but qualitatively different. J. Exp. Med. 191:695-702.