Department of Internal Medicine

Rheumatology Faculty

Craig Morita photo

Medical School:
University of California,
San Francisco

Residency:
University of California,
San Diego
Boston University

Fellowship:
Harvard Medical School
Brigham and Women's Hospital

Craig T. Morita, M.D., Ph.D.
Associate Professor
Fellowship Program Coordinator

My research focuses on gd T cells and nonpeptide antigens. gd T cells are a distinct subset of T cells that function as a bridge between innate and adaptive immunity by performing unique roles not played by ab T cells. Consistent with their unique functions, we have discovered that human gd T cells expressing V g 2V d 2 TCRs recognize nonpeptide antigens. The recognition of prenyl pyrophosphates is important in human immunity as evidenced by the large expansions of V g 2V d 2 T cells that occur in many different bacterial and parasitic infections. We purified two classes of nonpeptide antigens; prenyl pyrophosphates, small molecules required to make compounds such as cholesterol, and alkylamines, small molecules produced by some bacteria and found in certain foods. Non-Hodgkin's B cell lymphomas may also produce these molecules. We demonstrated that the gd TCR is used to recognize these compounds and that prenyl pyrophosphates are presented by a novel extracellular presentation pathway distinct from those used by MHC and CD1 proteins. Present studies focus on identifying novel antigen presenting molecules, isolating and determining the origin of new bacterial antigens, defining TCR regions required for recognition, and characterizing nonpeptide antigen responses in vivo with the ultimate goal of developing nonpeptide vaccines.

We also study a third class of nonpeptide antigens, lipids and glycolipids presented by CD1. CD1 proteins are MHC-like-molecules that are specialized for the presentation lipids. We now find that gd T cells in the major tissue subset recognize self and foreign lipids presented by CD1. We are isolating additional CD1-specific gd T cells, expressing their CD1-specific gd TCR, and identifying their lipid antigens.

A third area of study has focused on the adhesion and chemotaxis of gd T cells. Adhesion molecules and chemokine receptors determine the tissue homing capabilities of cells. gd T cells show specialized homing to epithelial surfaces and are enriched in areas of inflammation. We found that human gd T cells express ligands for E- and P-selectins, adhesion molecules that are upregulated in areas of inflammation. Now, we find that gd T cells express chemokine receptors not expressed by ab T cells. Our present studies focus on whether these differences explain the specialized homing properties of gd T cells.

Specific Areas of Interest

Honors, Awards, and Organizations

Recent Publications

  1. Tanaka Y, Morita CT, Tanaka Y, Nieves E, Brenner MB, Bloom BR. Natural and synthetic non-peptide antigens recognized by human gd T cells. Nature 1995; 375:155.
  2. Morita CT, Beckman EM, Bukowski JF, Tanaka Y, Band H., Bloom BR, Golan, DE, Brenner MB. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gd T cells. Immunity 1995; 3:495.
  3. Tanaka Y, Sano S, Nieves E, De Libero G, Rosa D, Modlin RL, Brenner MB, Bloom BR, Morita CT. Nonpeptide ligands for human gd T cells. Proc Natl Acad Sci USA 1994; 91:8175.
  4. Bukowski JF, Morita CT, Brenner MB. Human g d T cells recognize alkylamines derived from tea, edible plants, and microbes: implications for innate immunity. Immunity 1999; 11:57.
  5. Morita CT, Li H, Lamphear JG, Rich RR, Fraser JD, Mariuzza RA, Lee HK. Superantigen recognition by gd T cells: SEA recognition site for human V2 T cell receptors. Immunity 2001; 14:331.

Selected Reviews:

  1. Tanaka Y, Brenner MB, Bloom BR, Morita CT. Recognition of nonpeptide antigens by T cells. J Mol Med 1996; 74:223.
  2. Morita CT, Tanaka Y, Bloom BR, Brenner MB. Direct presentation of nonpeptide prenyl pyrophosphate antigens to human gd T cells. In "66th Forum in Immunology" (F. Plata). Res Immunol 1996; 147:73.
  3. Porcelli SA, Morita CT, Modlin RL. T-cell recognition of non-peptide antigens. Curr Opin Immunol 1996; 8:510.
  4. Chu DA, Morita CT, Weiss A. The Syk family of protein tyrosine kinases in T cell activation and development. Immunol. Reviews 1998; 165:167.
  5. Morita CT, Lee HK, Leslie DS, Tanaka Y, Bukowski JF, Märker-Hermann E. Recognition of nonpeptide prenyl pyrophosphate antigens by human g d T cells. Microbes and Infection 1999; 1:175.
  6. Morita CT, Mariuzza, RA, Brenner, MB. Antigen recognition by human gd T cells: pattern recognition by the adaptive immune system. Springer Sem Immunopath 2000; In press.

Links of Interest

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