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Research > Faculty By Division > Ted Hansen, PhD

Professor, Pathology and Immunology
Professor, Genetics
Room 8849, CSRB
Office: (314) 362-2716
Lab: (314) 362-2715
E-mail: hansen@wustl.edu
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Research

My lab studies antigen presentation by MHC-I molecules to CD8+ cytolytic T ymphocytes or CTL. CTL are the primary host defense against intracellular pathogens such as viruses and tumors. Immune surveillance by CTL is dependent upon the infected or malignant cells expressing foreign, antigenic peptides bound to self MHC-I molecules. We are currently investigating three outstanding questions relevant to antigen presentation by MHC-I molecules. These questions are:

1) How do herpesvirus gene products block antigen presentation? Most herpesviruses establish lifelong infections in their host and thus require immune evasion. During their co-evolution with their mammalian hosts, herpesviruses have evolved highly specialized immune evasion mechanisms that frequently block antigen presentation to CD8+ T cells. We are investigating immune evasion viral proteins from murine γ2-herpesvirus-68 (γHV68). Human Kaposi's sarcoma associated herpesvirus proteins specifically target MHC-I proteins and prevent CTL detection of infected cells.

2) What is the function of the novel class-I-like protein, MR1, in regulating mucosal immunity? MR1 is highly conserved MHC-I-like protein in mammals, that activates a unique population of T cells with an invariant T cell receptor. Interestingly the development of these MR1 activated T cells is dependent upon the commensal flora of the gut. Our experiments are using biochemical, cellular, transgenic and crystallographic approaches to determine the structure and function of MR1 proteins. These studies are being carried out in collaboration with the laboratories of Drs. Daved Fremont and Susan Gilfillan.

3) What is the role of antigen presentation in the development of CD8 T cells? We have engineered a class I molecule as a single chain trimer (SCT). When expressed as a transgene, the SCT allows us to study the development of T cells in presence of a single MHC-I molecule bound by a single peptide. This SCT mouse is a unique and powerful model system to define the precise role of antigen presentation during T cell development. In collaboration with the laboratory of Dr. Janet Connolly, we are currently using the SCT model to define the molecular basis by which T cell specificity is generated for self MHC bound by foreign peptides.

Editorial Responsibilities

2006 - PresentFaculty 1000Biology
2004 - PresentMember. Editorial BoardTransplantation
2004 - PresentEditorial BoardImmunology at Biology Direct
2002 - PresentAssociate EditorTissue Antigens
1993 - 1998Section EditorJournal of Immunology

Service to the University

2007 - PresentChair, Graduate Student Admissions for Immunology Program
2001 - 2004MSTP Committee
1998 - 2001Animal Studies Committee
1990 - PresentImmunology Program Steering Committee
1988 - 1999MSTP Committee
1985 - 1990Course Master, Medical Genetics

Selected Publications

Truscott SM, Lybarger L, Martinko JM, Mitaksov VE, Kranz DM, Connolly JM, Fremont DH, Hansen TH. Disulfide bond engineering to trap peptides in the MHC class I binding groove. J Immunol. 2007 May 15;178(10):6280-9, 2007 Abstract

Wang X, Herr RA, Chua WJ, Lybarger L, Wiertz EJ, Hansen TH. Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3. J Cell Biol. 2007 May 21;177(4):613-24. Epub 2007 May 14., 2007 Abstract

Hansen TH, Huang S, Arnold PL, Fremont DH. Patterns of nonclassical MHC antigen presentation. Nat Immunol. 2007 Jun;8(6):563-8, 2007 Abstract

Purtha WE, Myers N, Mitaksov V, Sitati E, Connolly J, Fremont DH, Hansen TH, Diamond MS. Antigen-specific cytotoxic T lymphocytes protect against lethal West Nile virus encephalitis. Eur J Immunol. 2007 Jul;37(7):1845-54, 2007 Abstract

Mitaksov V, Truscott SM, Lybarger L, Connolly JM, Hansen TH, Fremont DH. Structural engineering of pMHC reagents for T cell vaccines and diagnostics. Chem Biol. 2007 Aug;14(8):909-22., 2007 Abstract

Byun M, Wang X, Pak M, Hansen TH, Yokoyama WM. Cowpox virus exploits the endoplasmic reticulum retention pathway to inhibit MHC class I transport to the cell surface. Cell Host Microbe. 2007 Nov 15;2(5):306-15.Click here to read, 2007 Abstract


Current Trainees

Wei-Jen Chua
Sojung Kim
Roger Herr, PhD
Shouxiong Huang, PhD