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 Scopus citations

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

ASJC Scopus subject areas

  • Medicine(all)

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    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