Now that monoclonal antibodies are being used in clinical trials to modulate the immune response and to treat leukemias, we need to understand the relationship of the biological effect and the epitope reactivity of antibodies directed against a given macromolecule. Eight T cell specific surface molecules have been well characterized by monoclonal antibodies that react with peripheral blood T lymphocytes and T lymphocyte subpopulations. Multiple antibodies against each of these antigens have been created, and in most cases the antibodies react with several distinct epitopes. For example, eight distinct epitopes on the Tp32/45 antigen (OKT8, Leu-2) and three epitopes on the Tp19-29 antigen (OKT3, Leu-4) were defined by crossblocking studies and by reactivity with lymphocytes from 12 primate species (Clark, Martin, Hansen, and Ledbetter, unpublished results). We propose to study in more detail the biochemical structure of these two molecules. Both are composed of multiple subunits and are thought to be involved in T cell functions. We will utilize several approaches for analysis of the molecular structure, including (a) Peptide mapping to explore the relationship between the distinct subunits present in the Tp19-29 and Tp32/45 molecules; (b) Western blotting to identify the presence of epitopes on distinct subunits; and (c) metabolic labeling and pulse-chase studies on one and and two dimensional gels to explore precursor-product relationships between the subunits. We will relate these results to functional studies of anti Tp19-29 and anti-Tp32/45 antibodies.