The process of antigen presentation by MHC molecules allows T cells to samp
le the proteins expressed within a particular cell. This sampling is in the
form of short peptides bound within the grooves of MHC molecules displayed
on the surface of cells. In the context of immune surveillance, this prese
ntation allows the identification of infected cells by displaying peptides
originating from foreign proteins within the cell. However, MHC-bound pepti
des play additional roles beyond serving as antigenic stimuli during an imm
une response. In fact, it has become clear that MHC-bound peptides derived
from self proteins are critically involved in the development of T cells du
ring selective events in the thymus. In this review we will discuss the nat
ure of the population of MHC-bound peptides as it relates to thymocyte deve
lopment, with particular emphasis on the recent finding that peptide- MHC c
omplexes present at low levels can drive the positive selection of thymocyt
es.