Larry R. Pease, Ph.D.

Antigen presentation to T cells is a key event the course of a cellular immune response. Our laboratory has been investigating the interactions between T cells and antigen presenting cells with the goal of understanding this aspect of immune recognition at the molecular level, elucidating the regulatory events governing communication between lymphocyte and antigen presenting cells; and applying this emerging body of knowledge to modulate cellular immunity. Ongoing projects in this area include:

• Investigations on the impact of MHC class I structural diversity on the conserved T cell receptor:MHC contact sites along the molecular interface between ligand and receptor.
• Elucidation of the molecular events responsible for differential regulation of classical MHC class I genes during virus infection in the CNS.

Mechanisms of tolerance normally protect the body from autoimmune attack against healthy tissues. Cancers developing in the body are also protected from immune attack by these normal regulatory mechanisms.

We are seeking to understand tolerance mechanistically in the context of T cell receptor:MHC ligand interactions and to apply gained insights in the development of new ways of breaking immune tolerance for the treatment of cancer.

Ongoing studies in this area include:

• Development of virus vaccines that robustly activate cellular immunity, even in immune compromised hosts.
• Evaluating the relationship between strength of signal through the T cell receptor and T cell function in models of cancer immunity and type 1 diabetes.
• Define what variables in the expression of self proteins influence tolerance to those proteins.

Immune mechanisms are most commonly understood in the context of immune attack against pathogens, stressed cells, and even normal tissues in the course of autoimmunity. Less is understood about the importance of the immune response in healing. We have ongoing studies in the properties of IgM antibodies in promoting healing, particularly in the context of CNS injury.

Note:
After years of investigation, we learned our IgM antibody studies were compromised (refer to: Pease LR; Retraction. Induction of a gene expression program in dendritic cells with a cross-linking IgM antibody to the co-stimulatory molecule B7-DC. FASEBJ 2010;24:2135-2136).

After an extensive re-examination of the studies, the work on the immune modulatory properties of this IgM antibody have been stopped, and the related manuscripts retracted.