A kinetic threshold between negative and positive selection based on the longevity of the T cell receptor-ligand complex. J Exp Med 1999 May 17;189(10):1531-44
Date
05/20/1999Pubmed ID
10330432Pubmed Central ID
PMC2193645DOI
10.1084/jem.189.10.1531Scopus ID
2-s2.0-0033577859 (requires institutional sign-in at Scopus site) 98 CitationsAbstract
We have developed a unique in vivo system to determine the relationship between endogenous altered peptide ligands and the development of major histocompatibility complex class II- restricted T cells. Our studies use the 3.L2 T cell receptor (TCR) transgenic mouse, in which T cells are specific for Hb(64-76)/I-Ek and positively selected on I-Ek plus self-peptides. To this endogenous peptide repertoire, we have individually added one of six well-characterized 3.L2 ligands. This transgenic approach expands rather than constrains the repertoire of self-peptides. We find that a broad range of ligands produce negative selection of thymocytes in vivo. When compared with the in vitro TCR-ligand binding kinetics, we find that these negatively selecting ligands all have a half-life of 2 s or greater. Additionally, one of two ligands examined with no detectable binding to the 3.L2 TCR and no activity on mature 3.L2 T cells (Q72) enhances the positive selection of transgenic thymocytes in vivo. Together, these data establish a kinetic threshold between negative and positive selection based on the longevity of TCR-ligand complexes.
Author List
Williams CB, Engle DL, Kersh GJ, Michael White J, Allen PMAuthor
Calvin B. Williams MD, PhD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Cells, Cultured
Hemoglobins
Histocompatibility Antigens Class II
Hybridomas
Kinetics
Ligands
Mice
Mice, Transgenic
Muramidase
Peptide Fragments
Peptides
Protein Binding
Receptors, Antigen, T-Cell
Spleen
T-Lymphocytes
Thymus Gland