Mark M. Davis
Academic Appointments
- Professor, Microbiology & Immunology
- Member, Bio-X
- Member, Stanford Cancer Institute
Key Documents
Contact Information
- Academic Offices
Alternate Contact Rick Cuevas Administrative Assistant Email Tel Work 650-725-4755
Professional Overview
Administrative Appointments
- The Burt and Marion Avery Family Professor of Immunology, Stanford University School of Medicine (2007 - present)
- Director, Stanford Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine (2004 - present)
- Chair, Stanford University School of Medicine - Microbiology & Immunology (2002 - 2004)
Honors and Awards
- Milton and Francis Clauser Doctoral Prize, Caltech (1981)
- Passano Young Scientist Award, Passano Foundation (1985)
- Eli Lilly Award in Microbiology and Immunology, American Society of Microbiology (1986)
- Howard Taylor Ricketts Award, University of Chicago (1988)
- Gairdner Prize, Gairdner Foundation (1989)
- Member, National Academy of Sciences (1993)
Professional Education
| Ph. D.: | Caltech, Molecular Biology (1981) |
| B.A.: | The Johns Hopkins University, Molecular Biology (1974) |
Postdoctoral Advisees
Klas Erik Petter Brodin, David Furman, Arnold Han, Leo Hansmann, Huang Huang, Jun Huang, Helen McGuire, William O'Gorman, Florian Rubelt, Naresha Saligrama, Ruth Taniguchi, Fleur Tynan
Graduate & Fellowship Program Affiliations
Internet Links
Industry Relationships
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Scientific Focus
Current Research Interests
We are interested in the molecular basis of T and B lymphocyte recognition, as well as the control of differentiation and functional responses in these cells. In particular, we have studied the biochemical basis of T cell receptor binding to antigen/MHC complexes and find that the strength of the interactions is a very good predictor of what the resulting T cell response will be. We also find that T cell receptor-peptide/ MHC complexes have an inherent ability to form oligomers and that this could be part of the trigger for T cell activation. One spin-off of these biochemical studies has been the development of tetrameric peptide/MHC reagents which have proven to be generally useful for staining and characterizing antigen-specific T cells in complex mixtures of lymphocytes (i.e. McMichael and Callaghan, J. Exp. Med., 187:1367-1371, 1998). Among other things, we have used these tetramers to follow tumor specific T cells in patients with Melanoma and other cancers. In one patient where we see a substantial number of CD8+ T cells specific for a tumor antigen, the cells have no cytolytic activity and thus seem to have been anergized by the tumor. We are now working with a number of groups that have developed different vaccination strategies to determine which strategies are best able to produce a useful response.
Another important aspect of T cell recognition that is something of a black box is the mystery of what actually happens on the surface of T cell while it is surveying an antigen presenting cell. To investigate this we have made a large series of green fluorescent protein tagged cell surface molecules, expressed them in B or T lymphocytes and followed their movements using multi-color video microscopy. Thus far we find that many key molecules (ICAM-1, CD48, class II, MHC) on the B cell cluster to the interface with a T cell within seconds after the first rise in internal calcium (in the T cell) and the corresponding movement of complimentary membrane molecules on the T cell may be a key factor in the phenomenon of co-stimulation. That is, the augmentation of T cell responses that is characteristic of responses triggered in T cells when B cells, dendritic cells, or macrophages are the antigen presenting cells. Some of these videos can be seen at http://cmgm.stanford.edu/hhmi/mdavis.
Another area of interest is the structural basis of T cell receptor or antibody binding to their respective antigen/MHC or antigenic ligands. For some years we have noted the extreme sequence diversity in the V(D)-J regions of T cell receptors (the CDR3 loops) and proposed that these sequences are primarily responsible for peptide recognition. Recent X-ray structural analysis and other studies support this contention and suggest that the equivalent diverse CDR3 loops in immunoglobulins also play a key role in specificity determination.
Publications
- How the immune system talks to itself: the varied role of synapses. Immunol Rev. 2013; (1): 65-79
- Lineage structure of the human antibody repertoire in response to influenza vaccination. Sci Transl Med. 2013; (171): 171ra19
- Virus-specific CD4(+) memory-phenotype T cells are abundant in unexposed adults. Immunity. 2013; (2): 373-83
- Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity. 2012; (1): 142-52
- High-throughput, high-fidelity HLA genotyping with deep sequencing. Proc Natl Acad Sci U S A. 2012; (22): 8676-81
- Immunology taught by humans. Sci Transl Med. 2012; (117): 117fs2
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