How many signals are enough?

Abstract

The many signals that control the progress of various immune responses to both foreign and self antigens can be divided into no less than three major groups. The first group is the initial positive stimulus, associated with activation events through antigen receptors and their associated proteins. These signals launch lymphocytes in their response to antigen, either foreign or self. The second group of signals is negative and involves various end products and interactions between cells, all recognizing antigen. These signals are endogenous to the reacting cell, or nearly so (two interacting cells from the same clone, daughter cells, which are in the same locale and bind to the same ligand). The third group (the prevention of end product feedback, involving various forms of antigen presentation, T cell contributions, rheumatoid factor activity, and other mechanisms) is more likely to occur with nonself antigens, which are temporally and spatially more restricted than self antigens. Experimental evidence for this immunological schema is summarized and clarified in its relationship to the Bretscher-Cohn theory of self-nonself recognition and to suppressor cell and idiotype-antiidiotypic theories.