Figure 2: Consequences of TCR interactions with ligands of varying affinity in the thymus and periphery.

TCR–MHC interactions may facilitate maturation, survival, proliferation or death. The consequences of TCR binding to peptide–MHC are dictated by the affinity of the interaction, as well as the maturation state of the T cell. Immature thymocytes require a positively selecting signal, which is delivered through low-affinity interactions of their newly rearranged TCR with self-peptide–MHC. If no signal is delivered to the thymocyte because of an inability of the TCR to interact with self-peptide–MHC complexes, it will undergo programmed cell death known as death by neglect. Alternatively, a thymocyte may express a TCR that has high affinity for self-peptide–MHC. These cells must be eliminated by negative selection as they are potentially autoreactive. In the periphery mature T cells require low-affinity interactions with self-peptide–MHC to ensure survival. Furthermore, low-affinity interactions with self-peptide–MHC allow naı ¨ve T cells to expand when T-cell numbers are reduced. High-affinity interactions between a naı ¨ve T-cell in the periphery and peptide–MHC typically initiate the immune response against a foreign antigen. This leads to rapid proliferation and the development of the effector function culminating in the emergence of a few antigen-experienced cells that join the pool of memory T cells to await a subsequent encounter with antigen.