Two signal model of self/not-self immune discrimination: an update.

From a consideration of the evolution of the first immune systems in simple organisms, it is proposed that mechanisms for self/not-self discrimination evolved at an early stage of evolution in prototypic B cells, prior to separation of the B cell and T cell lineages. After passing an MHC protein-limited self/not-self discrimination gate, T cells depend for fine self/not-self discrimination either on B cells (extracellular discrimination) or on cells harbouring pathogens (intracellular discrimination). Full activation of B cells needs interaction with T cells, but this evolved late and is not part of the self/not-self decision.