Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery

Kazuyuki Kawamura, Karen Yao, Jacqueline A. Shukaliak-Quandt, Jaebong Huh, Mirza Baig, Laura Quigley, Naoko Ito, Antje Necker, Henry F. McFarland, Paolo A. Muraro, Roland Martin, Kouichi Ito

Research output: Contribution to journalArticle

Abstract

Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP111-129) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa 122. We previously found that ∼50% of human MBP111-129 (MBP122: Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP111-129 (MBP122:Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP111-129 (MBP122:Lys). We found that MBP111-129 (MBP122: Lys) is an antagonist for HD4-1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found that dual TCR expression exclusively facilitates the development of MBP111-129 TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it is not required for their development in the thymus. We also found that MS2-3C8 TCR Tg CD8 + T cells develop along with MS2-3C8 TCR Tg CD4 T cells, and that dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4 + and CD8+ T cells in the thymus and periphery, respectively. These results suggest that thymic and peripheral development of MBP-specific T cells are different; however, dual TCR expression can facilitate their development.

Original languageEnglish (US)
Pages (from-to)5462-5472
Number of pages11
JournalJournal of Immunology
Volume181
Issue number8
StatePublished - 2008
Externally publishedYes

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Myelin Basic Protein
Thymus Gland
T-Lymphocytes
Clone Cells
129 Strain Mouse
Immunodominant Epitopes
Transgenic Mice
Multiple Sclerosis

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Kawamura, K., Yao, K., Shukaliak-Quandt, J. A., Huh, J., Baig, M., Quigley, L., ... Ito, K. (2008). Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery. Journal of Immunology, 181(8), 5462-5472.

Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery. / Kawamura, Kazuyuki; Yao, Karen; Shukaliak-Quandt, Jacqueline A.; Huh, Jaebong; Baig, Mirza; Quigley, Laura; Ito, Naoko; Necker, Antje; McFarland, Henry F.; Muraro, Paolo A.; Martin, Roland; Ito, Kouichi.

In: Journal of Immunology, Vol. 181, No. 8, 2008, p. 5462-5472.

Research output: Contribution to journalArticle

Kawamura, K, Yao, K, Shukaliak-Quandt, JA, Huh, J, Baig, M, Quigley, L, Ito, N, Necker, A, McFarland, HF, Muraro, PA, Martin, R & Ito, K 2008, 'Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery', Journal of Immunology, vol. 181, no. 8, pp. 5462-5472.
Kawamura, Kazuyuki ; Yao, Karen ; Shukaliak-Quandt, Jacqueline A. ; Huh, Jaebong ; Baig, Mirza ; Quigley, Laura ; Ito, Naoko ; Necker, Antje ; McFarland, Henry F. ; Muraro, Paolo A. ; Martin, Roland ; Ito, Kouichi. / Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery. In: Journal of Immunology. 2008 ; Vol. 181, No. 8. pp. 5462-5472.
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abstract = "Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP111-129) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa 122. We previously found that ∼50{\%} of human MBP111-129 (MBP122: Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP111-129 (MBP122:Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP111-129 (MBP122:Lys). We found that MBP111-129 (MBP122: Lys) is an antagonist for HD4-1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found that dual TCR expression exclusively facilitates the development of MBP111-129 TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it is not required for their development in the thymus. We also found that MS2-3C8 TCR Tg CD8 + T cells develop along with MS2-3C8 TCR Tg CD4 T cells, and that dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4 + and CD8+ T cells in the thymus and periphery, respectively. These results suggest that thymic and peripheral development of MBP-specific T cells are different; however, dual TCR expression can facilitate their development.",
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AU - Kawamura, Kazuyuki

AU - Yao, Karen

AU - Shukaliak-Quandt, Jacqueline A.

AU - Huh, Jaebong

AU - Baig, Mirza

AU - Quigley, Laura

AU - Ito, Naoko

AU - Necker, Antje

AU - McFarland, Henry F.

AU - Muraro, Paolo A.

AU - Martin, Roland

AU - Ito, Kouichi

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N2 - Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP111-129) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa 122. We previously found that ∼50% of human MBP111-129 (MBP122: Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP111-129 (MBP122:Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP111-129 (MBP122:Lys). We found that MBP111-129 (MBP122: Lys) is an antagonist for HD4-1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found that dual TCR expression exclusively facilitates the development of MBP111-129 TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it is not required for their development in the thymus. We also found that MS2-3C8 TCR Tg CD8 + T cells develop along with MS2-3C8 TCR Tg CD4 T cells, and that dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4 + and CD8+ T cells in the thymus and periphery, respectively. These results suggest that thymic and peripheral development of MBP-specific T cells are different; however, dual TCR expression can facilitate their development.

AB - Myelin basic protein (MBP)-specific T cells are thought to play a role in the development of multiple sclerosis. MBP residues 111-129 compose an immunodominant epitope cluster restricted by HLA-DRB1*0401. The sequence of residues 111-129 of MBP (MBP111-129) differs in humans (MBP122:Arg) and mice (MBP122:Lys) at aa 122. We previously found that ∼50% of human MBP111-129 (MBP122: Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP111-129 (MBP122:Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP111-129 (MBP122:Lys). We found that MBP111-129 (MBP122: Lys) is an antagonist for HD4-1C2 TCR, therefore, MS2-3C8 and HD4-1C2 TCRs are agonist- and antagonist-specific TCRs in mice, respectively. Therefore, we examined the development of HD4-1C2 TCR and MS2-3C8 TCR transgenic (Tg) T cells in the thymus and periphery. We found that dual TCR expression exclusively facilitates the development of MBP111-129 TCR Tg T cells in the periphery of HD4-1C2 TCR/HLA-DRB1*0401 Tg mice although it is not required for their development in the thymus. We also found that MS2-3C8 TCR Tg CD8 + T cells develop along with MS2-3C8 TCR Tg CD4 T cells, and that dual TCR expression was crucial for the development of MS2-3C8 TCR Tg CD4 + and CD8+ T cells in the thymus and periphery, respectively. These results suggest that thymic and peripheral development of MBP-specific T cells are different; however, dual TCR expression can facilitate their development.

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