The anatomy of T-cell activation and tolerance

A. Mondino, A. Khoruts, M. K. Jenkins

Research output: Contribution to journalArticlepeer-review


The mammalian immune system must specifically recognize and eliminate foreign invaders but refrain from damaging the host. This task is accomplished in part by the production of a large number of T lymphocytes, each bearing a different antigen receptor to match the enormous variety of antigens present in the microbial world. However, because antigen receptor diversity is generated by a random mechanism, the immune system must tolerate the function of T lymphocytes that by chance express a self-reactive antigen receptor. Therefore, during early development, T cells that are specific for antigens expressed in the thymus are physically deleted. The population of T cells that leaves the thymus and seeds the secondary lymphoid organs contains helpful cells that are specific for antigens from microbes but also potentially dangerous T cells that are specific for innocuous extrathymic self antigens. The outcome of an encounter by a peripheral T cell with these two types of antigens is to a great extent determined by the inability of naive T cells to enter nonlymphoid tissues or to be productively activated in the absence of inflammation.

Original languageEnglish
Pages (from-to)2245-2252
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number6
Publication statusPublished - Mar 19 1996

ASJC Scopus subject areas

  • Genetics
  • General


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