Ligand-specific selection of MHC class II-restricted thymocytes in fetal thymic organ culture. J Immunol 2000 Jun 01;164(11):5675-82
Date
05/23/2000Pubmed ID
10820243DOI
10.4049/jimmunol.164.11.5675Scopus ID
2-s2.0-0034114928 (requires institutional sign-in at Scopus site) 10 CitationsAbstract
Positive and negative selection of thymocytes is determined by the specificity of the TCR and signaling through its associated molecules. We have studied selection of thymocytes bearing a MHC class II-restricted TCR using fetal thymic organ culture. This system allows the addition of peptides to the already diverse panoply of endogenous peptide ligands and is useful for analyzing ligand-specific negative selection of CD4 single positive (CD4SP) thymocytes. The data reveal that the ability of a given ligand to mediate negative selection is related to its dissociation rate from the TCR. We find that negative selection is very sensitive, and only the weakest ligand that we can identify fails to induce negative selection. None of the numerous peptides tested were able to induce an increase in CD4SP thymocytes. In addition, the ligands that induce negative selection of CD4SP thymocytes also cause an increase in numbers of CD8SP thymocytes bearing high levels of the class II-restricted TCR. Although these cells have a cell surface phenotype consistent with positive selection, they most likely represent cells in the process of negative selection. Further analysis reveals that these cells are not induced by these ligands in intact adult animals and that their induction is probably only revealed in the organ culture system.
Author List
Kersh GJ, Engle DL, Williams CB, Allen PMAuthor
Calvin B. Williams PhD, MD Chief, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid SubstitutionAnimals
CD8-Positive T-Lymphocytes
Epitopes, T-Lymphocyte
Fetus
Hemoglobins
Histocompatibility Antigens Class II
Ligands
Lymphocyte Activation
Mice
Mice, Inbred AKR
Mice, Inbred C57BL
Mice, Transgenic
Oligopeptides
Organ Culture Techniques
Receptors, Antigen, T-Cell
T-Lymphocyte Subsets
Thymus Gland
