Open AccessT cell positive selection by a high density, low affinity ligand
Author(s) -
Chih-Pin Liu,
Frances Crawford,
Philippa Marrack,
John W. Kappler
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.8.4522
Subject(s) - major histocompatibility complex , t cell receptor , negative selection , ligand (biochemistry) , peptide , affinities , biology , receptor , t cell , mhc restriction , repertoire , microbiology and biotechnology , mhc class i , chemistry , antigen , immunology , biochemistry , immune system , gene , genome , physics , acoustics
Interaction of the αβ T cell receptor (TCR) with major histocompatibility (MHC) molecules occupied with any of a large collection of peptides derived from self proteins is a critical step in driving T cell “positive” selection in the thymus. Interaction with this same pool of self-peptide/MHC ligands deletes T cells with potential self-reactivity. To examine how T cells survive both of these processes to form a self-tolerant mature repertoire, mice were constructed whose entire class II MHC IEk specific repertoire was positively selected on a single peptide covalently attached to the IEk molecule. In these mice T cells were identified that could respond to a variant of the positively selecting peptide bound to IEk . The affinities of the TCRs from these T cells for the positively selecting ligand were extremely low and at least 10-fold less than those for the activating ligand. These results support the theory that positive selection is driven by TCR affinities lower than those involved in T cell deletion or activation and that, if present at high concentration, even very low affinity ligands can positively select.