Effective immunity to infectious agents requires the initial recognition of antigen by specific receptors, which leads to the activation of immunocytes and the elicitation of an immune response. Because T cell antigen recognition and directed responses are complex processes, they are initiated and quelled in a highly regulated manner. Our laboratory has focused on defining the molecular processes that control T cell antigen presentation and recognition. Research in this area is focused on determining the chemical nature of antigens displayed by Major histocompatibility, complex (MHC)-encoded class I molecules and the nonclassical class I-like protein CD1d. Quantitative aspects of antigen presentation and recognition are also being studied to determine how these factors control the initiation of a T cell response. Our studies provide insights into the biochemical basis of T cell antigen recognition and response as well as the molecular processes underlying the initiation and regulation of immune responses by CD1d-restricted natural T lymphocytes.