An ‘antigenic ligand competition’ model for antigen receptor-mediated lymphocyte selection

Abstract

The 'antigenic ligand competition' model advanced herein represents a principally novel view on lymphocyte selection, postulating a leading role in this process of competition between different determinants expressed on self ligands for binding to antigen receptors. Based on the data indicating that cell viability and cell growth are separately regulated processes, it is speculated that the binding of antigenic receptors with monovalent determinants (MDs) expressed on soluble self ligands may be responsible for lymphocyte survival, whereas the moderate (but not hyper) cross-linking of antigenic receptors with polyvalent determinants (PDs) expressed on other or the same self ligands may provide signalling that is necessary to trigger lymphocyte proliferation. In the light of the model, the lymphocytes whose receptors bind with high affinity to self MDs survive, while not receiving a proliferative stimulus. On the other hand, those lymphocytes whose receptors interact with high affinity with self PDs and consequently undergo hypercross-linking die by apoptosis. Lastly, those lymphocytes whose receptors interact simultaneously with both MDs and PDs in a balanced competitive manner receive both viability and a proliferative stimulus and, as a consequence, it is only they which obtain selective advantage. The balanced competition between self MDs and self PDs for receptor binding seems likely when the receptors have relatively low affinity to such determinants inasmuch as the opposite, namely comparably high specificity (affinity) to structurally distinct determinants, is unlikely. Essentially, the model presented herein also suggests that a balance between distinct antigenic determinants occupying antigen receptors may determine not only self antigen-driven lymphocyte selection, but also immune reactivity of the functionally mature B- and T-cells which have passed through this selection.