Positive selection in the thymus: An enigma wrapped in a mystery

摘要

One of the many mysteries that loomed over the field of immunology in its dark ages (that period prior to characterization of the TCR and peptide binding by MHC molecules) was the process of T cell development and selection of the receptor repertoire in the thymus. The work of Hogquist and colleagues was the culmination of theoretical and experimental work starting decades earlier (1, 2), and it established a clear vision of the enigmatic process known as "positive selection" (3). The first and most famous observation, which drove the field, was that T cells did not recognize Ags as such, but rather as some combination of Ag and allelic variations of MHC class II molecules (4, 5) or MHC class I Ags (6-8). "MHC restriction" was magic enough, but there soon emerged an even more perplexing concept that appeared to separate the recognition of Ag from that of MHC molecules.