Amnon Altman, Ph.D., and his team study T lymphocytes—white blood cells formed in the thymus that are essential in the body’s fight against infection and disease. In particular, they study the biochemical changes that occur in T lymphocytes when an antigen (a substance that can cause an immune response) activates a binding site on the surface of the T cell, called the T Cell Antigen Receptor (TCR).
T cells mediate important functions in the immune system and are responsible for major types of immune defense responses against bacteria and viruses and against cancer. Because of the central importance to immunity that T cells play, aberrations in their activation process can prevent the immune system from being effective, or can lead to immunological diseases. For example, T cells that react in an abnormally strong manner or expand to exceedingly large numbers can cause undesired effects in the form of autoimmune diseases and harmful inflammation.
Dr. Altman and his laboratory have already identified several proteins critical to the proper activation of T cells. Notable among these is an enzyme called protein kinase C theta (PKCθ), which is essential for T cell activation and survival. Understanding this protein, and others like it, will help in the development of immune therapies, new treatments for autoimmune diseases, and increase the chances for long-term survival of organ transplants. More recent work in the lab resulted in the discovery of a novel activation pathway that operates in regulatory T cells, a T cell subset whose primary role is to prevent excessive immune responses that carry the risk of autoimmunity and inflammation. However, the same regulatory T cells can also have the undesired effect of inhibiting immune responses against growing cancers. Rational manipulation of this pathway could result in enhanced tumor immunity, thereby facilitating the killing of tumor cells by the immune system. Indeed, Dr. Altman and his lab members have demonstrated that genetic deletion of a critical enzyme required for the immune inhibitory activity of Treg cells enhances the immune response against growing tumors in mice, resulting in a significantly reduced tumor growth.
A Novel CTLA4-Mediated Treg Cell-Intrinsic Signaling Pathway
Recent work by others has provided evidence that, in contrast to conventional T cells, PKCq negatively regulates the suppressive activity
PKC enzymes play critical roles in the differentiation and proliferation of many cell types, including T cells, and in the response to diverse stimuli.
SLAT, a T Cell-Specific Signaling Protein
In 2003, we reported the isolation and initial characterization of a novel signaling protein, termed SWAP-70-Like Adaptor of T cells
From the lab
LA JOLLA, CA—Follicular helper T cells (Tfh cells), a rare type of T cells, are indispensible for the maturation of
Awards & Honors
- Leukemia Society of America, Inc., Scholarship Award, 1983
- American Cancer Society's Junior Faculty Research Award, 1979
- National Cancer Institute Young Investigator Research Award, 1978