A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE.
Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis. Immunization of B10.PL mice with the Ac1-9 peptide, the immunodominant determinant of myelin basic protein (MBP), produced a single episode of EAE followed by recovery and resistance to reinduction of disease. Using the CDR3 length spectratyping technique, we characterized the clonal composition of the Ac1-9-specific T cell repertoire from induction through onset and resolution of disease. Two clonally restricted subsets within a heterogeneous self-reactive repertoire were found in mouse lymph nodes, spleen, and spinal cord soon after immunization, before any sign of EAE. These clonotypes, designated BV8S2/BJ2S7 and BV16/BJ2S5, were present in all mice examined and thus considered public. BV8S2/BJ2S7 was found in far greater excess; was exclusively Th1 polarized; disappeared from the spinal cord, spleen, and lymph nodes concomitantly with recovery; and transferred disease to naive recipients. In contrast, BV16/BJ2S5 and numerous private clonotypes were either Th1 or Th2 and persisted following recovery. These results are consistent with the hypothesis that the public clonotype BV8S2/BJ2S7 is a driver of disease and necessary for its propagation.
Menezes
Juscilene S
JS
Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, San Diego, California 92121, USA.
van den Elzen
Peter
P
Thornes
Jordan
J
Huffman
Donald
D
Droin
Nathalie M
NM
Maverakis
Emanual
E
Sercarz
Eli E
EE
D000818:Animals; D022801:Complementarity Determining Regions / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D051379:Mice; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000633:toxicity; D020127:Recovery of Function / Q000235:genetics / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000473:pathology
D022801:Complementarity Determining Regions; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C074815:myelin basic protein 1-9