Positive selection as a developmental progression initiated by alpha beta TCR signals that fix TCR specificity prior to lineage commitment.
During positive selection, immature thymocytes commit to either the CD4+ or CD8+ T cell lineage ("commitment") and convert from short-lived thymocytes into long-lived T cells ("rescue"). By formal precursor-progeny analysis, we now identify what is likely to be the initial positive selection step signaled by alpha beta TCR, which we have termed "induction". During induction, RAG mRNA expression is downregulated, but lineage commitment does not occur. Rather, lineage commitment (which depends upon the MHC class specificity of the alpha beta TCR) only occurs after downregulation of RAG expression and the consequent fixation of alpha beta TCR specificity. We propose that positive selection can be viewed as a sequence of increasingly selective developmental steps (induction-->commitment-->rescue) that are signaled by alpha beta TCR engagements of intrathymic ligands.
Bhandoola
A
A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cibotti
R
R
Punt
J A
JA
Granger
L
L
Adams
A J
AJ
Sharrow
S O
SO
Singer
A
A
D000818:Animals; D017252:CD3 Complex / Q000502:physiology; D018956:CD5 Antigens / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015536:Down-Regulation / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism
D017252:CD3 Complex; D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein