Identification of a Naturally Occurring Ligand for Thymic Positive Selection

• Published in: Immunity (Cambridge, Mass.) Vol. 6; no. 4; pp. 389 - 399
• Main Authors: Hogquist, Kristin A, Tomlinson, Andy J, Kieper, William C, McGargill, Maureen A, Hart, Marilyn C, Naylor, Stephen, Jameson, Stephen C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-1997
• Subjects: Actin Depolymerizing Factors; Actins - metabolism; Amino Acid Sequence; Animals; CD4 Antigens - analysis; CD8 Antigens - analysis; Cell Communication - immunology; Cell Differentiation - immunology; Destrin; Epithelium - metabolism; Fetus; H-2 Antigens - analysis; Ligands; Lymphocyte Count; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microfilament Proteins - analysis; Microfilament Proteins - immunology; Microfilament Proteins - metabolism; Organ Culture Techniques; Peptides - immunology; Peptides - pharmacology; T-Lymphocyte Subsets - chemistry; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - metabolism; Thymus Gland - chemistry; Thymus Gland - cytology; Thymus Gland - metabolism
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80282-4

In the thymus, positive and negative selection shape the T cell repertoire. It has previously been shown that positive selection, like negative selection, is the result of the interaction of the TCR with self-peptides bound to MHC. However, little is known about the number or nature of the self-peptide ligands that mediate positive selection in vivo. We devised a novel assay with enhanced sensitivity for low affinity TCR ligands to identify self-peptides that may be biologically relevant. At least eight K
b-bound self-peptides were detected by this assay using thymocytes bearing the OT-I TCR (specific for OVAp/K
b). The sequence of one of these peptides was determined using the recently developed technique of membrane preconcentration-capillary electrophoresis-tandem mass spectrometry. This peptide, CPα1, has limited sequence similarity to OVAp, yet was found to induce positive selection of OT-I thymocytes in fetal thymic organ culture.