T cell positive selection by a high density, low affinity ligand.

Abstract:

:Interaction of the alpha beta 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.

authors

Liu CP,Crawford F,Marrack P,Kappler J

doi

10.1073/pnas.95.8.4522

subject

Has Abstract

pub_date

1998-04-14 00:00:00

pages

4522-6

issue

8

eissn

0027-8424

issn

1091-6490

journal_volume

95

pub_type

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