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 Maverakis, Eli E. Sercarz
Juscilene S. Menezes, Peter van den Elzen, Jordan Thornes, Donald Huffman, Nathalie M. Droin, Emanual Maverakis, Eli E. Sercarz
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Research Article Immunology

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

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.

Authors

Juscilene S. Menezes, Peter van den Elzen, Jordan Thornes, Donald Huffman, Nathalie M. Droin, Emanual Maverakis, Eli E. Sercarz

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Figure 3

Immunologic features of public clonotypic expansions.

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Immunologic features of public clonotypic expansions. Analysis of mRNA e...
Analysis of mRNA expression of the public expansions by real-time PCR was performed (A) from draining lymph node cells of individual mice collected 4 and 8 days after immunization, followed by restimulation in vitro with Ac1–9 for 3 days, or (B) from spinal cord cells of individual mice collected 8 and 14 days after immunization without in vitro stimulation. Symbols represent individual samples; mean expression is denoted by horizontal bars, and mean values are shown. After 6 (C) or 48 (D and E) hours in culture, pooled cells from the draining lymph nodes and spleen of individual mice, 8 days after immunization, were sorted with antibodies to different surface markers using magnetic beads and analyzed by immunoscope, as described in Methods. Results are representative of 4 independent experiments. mFasL.1, mouse FasL.1.