Michael Kuhns, PhD

Assistant Professor, Immunobiology

Contact

• Medicial Research Building, Room 224
• Phone: (520) 626-6461
• Email: mkuhns@email.arizona.edu

Education

• Stanford University - Postdoctoral Fellow
• The University of California at Berkeley - PhD
• The University of Arizona – BS

Research

For all vertebrates, from mice to humans, vaccine-induced and naturally primed immunity to pathogens require that coordinated, multi-cellular responses emerge from a myriad of ‘conversations’ that take place between cells of the immune system. These conversations occur via cytokines and chemokines that are secreted by one cell and detected via receptors on other cells. They also occur via direct contacts between membrane-bound molecules at the interface between two cells. Ultimately, these conversations are responsible for insuring that an appropriate immune response occurs in the appropriate place, and at the appropriate time, to fight an infection without inducing an inappropriate response to commensal organisms or self-antigens.

The molecules on T cells that are involved in these conversations include but are not limited to: the T cell receptor (TCR), which provides clonotypic antigen specificity to T cells; the CD3δε , γε , and ζζ signaling dimers that connect the TCR to the intracellular signaling machinery; the CD8 and CD4 coreceptors that provide major histocompatibility molecule (MHC)-restriction for T cells that recognize antigenic peptides bound to class I or II MHC, respectively; and costimulatory molecules, such as CD28, that provide information about the activation state of an antigen presenting cell (APC) and thus the context in which an antigen occurs. We are interested in understanding how the individual contributions from this chorus of molecules are integrated to achieve the critical balance between tolerance of self-antigens and protective immunity against pathogenic infection.

Specifically, we are working to understand how the information that is critical for T cells to decide if and how they should respond to antigen is conveyed from an APC to a T cell. We are using a variety of classic molecular, cellular, and biochemical techniques, as well as more modern live cell imaging approaches, to probe the molecular mechanisms involved in these processes. We are also developing mouse model systems to determine how individual mechanisms contribute to T cell responses in vivo during pathogenic infection or autoimmunity. Altogether, our work is aimed at increasing our basic and practical appreciation of T cell responses and regulation.

Selected Publications

• Michael S. Kuhns, Andrew T. Girvin, Lawrence O. Klein, Rebecca Chen, Kirk D.C. Jensen, Evan W. Newell, Johannes B. Huppa, Björn F. Lillemeier, Morgan Huse, Yueh-hsiu Chien, K. Christopher Garcia and Mark M. Davis (2010). Evidence for a functional sidedness to the abTCR. PNAS 107:5094-5099. PMID: 20202921.

• Michael S. Kuhns and Mark M. Davis (2007). Disruption of Extracellular Interactions Impairs T Cell Receptor-CD3 Complex Stability and Signaling. Immunity 26:357-369. PMID: 17368054.

• Michael S. Kuhns, Mark M. Davis, and K. Christopher Garcia (2005). Deconstructing the Form and Function of the TCR/CD3 Complex. Immunity 24:133-139. PMID: 16473826.

• Morgan Huse, Lawrence O. Klein, Andrew T. Girvin, Joycelyn M. Faraj, Qi-Jing Li, Michael S. Kuhns, and Mark M. Davis (2007). Spatial and Temporal Dynamics of T Cell Receptor Signaling Using a Photoactivatable Agonist. Immunity 27:76-88. PMID: 17629516.

• Jackson G. Egen, Michael S. Kuhns, and James P. Allison (2002). CTLA-4: new insights into its biological function and use in tumor immunotherapy. Nature Immunology 3(7):611-618. PMID: 12087419.

• Cynthia A. Chambers, Michael S. Kuhns, Jackson G. Egen, and James P. Allison (2001). CTLA-4 mediated inhibition in Regulation of T cell responses:  Mechanisms and Manipulation in Tumor Immunotherapy.  Annu. Rev. Immunol. 19:565-594. PMID: 11244047.

• Michael S. Kuhns, Victoria Epshteyn, Raymond A. Sobel and James P. Allison (2000).  CTLA-4 Regulates the Size, Function, and Reactivity of a Primed Pool of CD4+ T Cells.  PNAS 97(23):12711-12716. PMID: 11050166.

Peer-Reviewed Publications

Click here to see a listing of peer-reviewed publications