Last Updated: 12/16/2008

Jeffrey A Frelinger, PhD Kenan Professor Immunology

Research Interests
Work in our laboratory is focused on understanding how major histocompatibility complex (MHC) molecules function in the immune response to pathogens. This simple question involves the most fundamental aspect of immunology: self/non-self discrimination. Our work uses a wide variety of biophysical, biochemical and immunological approaches. We have focused our attention on the interaction of class I MHC molecules the peptides they bind and the T cell receptor. We are fascinated with the question of immunodominance-How does the immune system choose which peptides to respond to out of the array present during virus infection and why does it change over the course of an immune response. We use a variety of systems, to address this problem. We study the response of mice to the Lymphocytic choriomeningitis virus and the bacterial pathogen Francisella tularensis. Our studies range from structural biology (in collaboration with Ed Collins) to clinical interventions using tumor immunology (with Jon Serody). As we enter the era of immunology applied to infectious disease organisms we face new challenges. Biodefense and emerging infectious disease are of course the same thing. They differ only in the way the organism is introduced- accidentally or on purpose. The questions are the same. We believe the coming years will expand our knowledge and ability to cope with new infectious diseases as well as remerging disease in new and effective ways.

How are these studies related to cancer? The regulation of immune responses is critical to understanding the immune response to tumors. CD8+ T cells are essential in mounting anti tumor responses. The affinity and avidity of TCR MHC interactions plays a pivotal role in the decision of an individual T cell to respond or not and no doubt plays the same role in the lack of responsiveness to self antigens. Tumor antigens (except for viral antigens) are self antigens. The immune response to viruses is obviously critically related to the prevention and treatment of tumors caused by oncogneic viruses.

Recent Accomplishments and Honors
Elected to American Association of Immunologists Council.

Publications
Wong, CP, L. Li, JA Frelinger, and R. Tisch. Early Autoimmune Destruction of Islet Grafts Is Associated with a Restricted Repertoire of IGRP-Specific CD8+ T Cells in Diabetic Nonobese Diabetic Mice. J. Immunol. 176:1637, 2006.
Maile, R., CM Barnes, AI Nielsen, , AA Meyer, , JA Frelinger, and BA Cairns,. Lymphopenia-induced homeostatic proliferation of CD8+ T cells is a mechanism for effective allogeneic skin graft rejection following injury. J. Immunol. 113:2888, 2006.
Wong, C. R. Stevens, B. Long, L. Li, M. Wallet, K. Goudy, J. Frelinger and R. Tisch. Identical beta cell-specific CD8+ T cell clonotypes typically reside in both PBL and pancreatic islets. J. Immunol. 178:1388, 2007.
Woolard, M., J. Wilson, L. Hensley, L. Jania, T. Kawula, J. Drake and J. Frelinger. Francisella tularensis-Infected Macrophages Release Prostaglandin E2 that Blocks T Cell Proliferation and Promotes a Th2-Like Response. J Immunol 178:2065, 2007.
P. Hess, C. Barnes, M. Woolard, M. Johnson, J. Cullen, E. Collins and J. Frelinger. Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein, saporin. Blood, 109:3300, 2007.
S. Tian, R. Maile, E. Collins and J. Frelinger. CD8+ T cell activation is governed by TCR-pMHC affinity, not dissociation rate. J. Immunol.179:2952, 2007.
157. D.S. Riddle, P.J. Miller, B.G. Vincent, M.D. Darrow, K.K. Tsui, R. Maile, J.A. Frelinger, and E.J. Collins. Rescue of Cytotoxic Function in the CD8 Knockout Mouse by Removal of MHC II During Selection. Eur. J. Immunol. 38:1511, 2008.
158. M.D. Woolard, L.L. Hensley, T.H. Kawula and J.A. Frelinger. Respiratory Francisella tularensis Live Vaccine Strain infection induces Th17 cells and prostaglandin E2 that inhibits generation of IFN-+ T cells. Infection and L. Li, B. Wang, JA Frelinger, R. Tisch. T cell promiscuity in autoimmune diabetes. Diabetes, 57:2099, 2008.
Frelinger JA. Novel epitope begets a novel pathway in type 1 diabetes progression. J Clin Invest. 2008 Oct;118(10):3268-71.
Hall, JD, Woolard, MD, Gunn, BN Craven, R, Taft-Benz, S, Frelinger, JA and Kawula, TH. Cellular response and infected host cell repertoire of Francisella tularensis LVS, Schu S4 and subspecies novicida infected lungs. Infect Immun. 2008 DOI:10.1128/IAI.01176-08. PMID: 18852251

E-mail: jfrelin@med.unc.edu
Telephone: (919) 966-2599
FAX: (919) 962-8103
Address: 609A/804 Mary Ellen Jones Bldg, CB# 7290 Chapel Hill, NC 27599-7290

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