Identification of a naturally occurring ligand for thymic positive selection.
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, CP alpha1, has limited sequence similarity to OVAp, yet was found to induce positive selection of OT-I thymocytes in fetal thymic organ culture.
Hogquist
K A
KA
Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis 55455, USA.
Tomlinson
A J
AJ
Kieper
W C
WC
McGargill
M A
MA
Hart
M C
MC
Naylor
S
S
Jameson
S C
SC
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D051345:Destrin; D004848:Epithelium / Q000378:metabolism; D005333:Fetus; D006183:H-2 Antigens / Q000032:analysis; D008024:Ligands; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000032:analysis* / Q000276:immunology / Q000378:metabolism*; D009924:Organ Culture Techniques; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*; D013950:Thymus Gland / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism*
D051339:Actin Depolymerizing Factors; D000199:Actins; D015704:CD4 Antigens; D016827:CD8 Antigens; D051345:Destrin; D006183:H-2 Antigens; D008024:Ligands; D008840:Microfilament Proteins; D010455:Peptides