A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE

Juscilene S. Menezes, Peter Van Den Elzen, Jordan Thornes, Donald Huffman, Nathalie M. Droin, Emanual Michael Maverakis, Eli E. Sercarz

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2176-2185
Number of pages10
JournalJournal of Clinical Investigation
Volume117
Issue number8
DOIs
StatePublished - Aug 1 2007

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Autoimmune Experimental Encephalomyelitis
T-Lymphocytes
Immunization
Spinal Cord
Spleen
Lymph Nodes
Immunodominant Epitopes
Myelin Basic Protein
Multiple Sclerosis
Animal Models
Peptides

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Menezes, J. S., Van Den Elzen, P., Thornes, J., Huffman, D., Droin, N. M., Maverakis, E. M., & Sercarz, E. E. (2007). A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE. Journal of Clinical Investigation, 117(8), 2176-2185. https://doi.org/10.1172/JCI28277

A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE. / Menezes, Juscilene S.; Van Den Elzen, Peter; Thornes, Jordan; Huffman, Donald; Droin, Nathalie M.; Maverakis, Emanual Michael; Sercarz, Eli E.

In: Journal of Clinical Investigation, Vol. 117, No. 8, 01.08.2007, p. 2176-2185.

Research output: Contribution to journalArticle

Menezes, JS, Van Den Elzen, P, Thornes, J, Huffman, D, Droin, NM, Maverakis, EM & Sercarz, EE 2007, 'A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE', Journal of Clinical Investigation, vol. 117, no. 8, pp. 2176-2185. https://doi.org/10.1172/JCI28277
Menezes, Juscilene S. ; Van Den Elzen, Peter ; Thornes, Jordan ; Huffman, Donald ; Droin, Nathalie M. ; Maverakis, Emanual Michael ; Sercarz, Eli E. / A public T cell clonotype within a heterogeneous autoreactive repertoire is dominant in driving EAE. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 8. pp. 2176-2185.
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