Michael Julius

Molecular interactions regulating T lymphocyte activation

The activation and effector functions of thymus-derived T-lymphocytes are central to the induction and regulation of cellular and humoral immune responses against antigen. In physiological circumstances, antigen specific T-cell activation is initiated through the TcR/CD3 complex. The clonotypic antigen recognition unit of this complex (TcR) is comprised of two polymorphic, disulfide linked proteins. The membrane expression, and signaling function of this heterodimer require its non-covalent association with at least four monomorphic proteins, collectively termed the CD3 complex.

Recent studies have demonstrated that a number of other membrane molecules, while not directly contributing to T-cell antigen specificity, provide signals which modify and supplement those induced through the TcR/CD3 complex. As a group, these molecules have been termed "accessory activation molecules", with CD4, CD8, CD28, and CD45 membrane glycoproteins considered the most prominent members to date. The effects of these molecules on TcR/CD3 signaling can be extreme, resulting in T cell growth, anergy, or death.

The object of our research is to elucidate the pre-requisite ordered interactions of these accessory activation molecules with the TcR/CD3 complex in support of T cell activation. Toward this end we are characterizing the physical interactions among these molecules, and establishing the biochemical mechanisms through which these molecules, individually and/or in combination, alter the coupling of the TcR/CD3 complex to intra-cellular second messenger generating systems.

Characterization of a novel B-lymphocyte growth and differentiation factor

We have isolated a novel B-tropic cytokine from colostrum and early milk of lactating humans and cows. Lactation-Associated-Immuno-Tropic (LAIT)-protein is functionally distinct from all heretofore characterized cytokines in that, in isolation, it supports the growth and differentiation of resting B-cells. Our goals are to identify the cell(s) which secrete LAIT-protein, as well as characterizing the agents which induce this process. Further, the isolation and preparation of antibodies to the B-cell membrane receptor for LAIT-protein will enable an analysis of the biochemistry of signal transduction induced upon ligand-receptor interaction.