Different development of myelin basic protein agonist- and antagonist-specific human TCR transgenic T cells in the thymus and periphery.
J Immunol
; 181(8): 5462-72, 2008 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-18832703
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 (MBP(111-129)) differs in humans (MBP122Arg) and mice (MBP122Lys) at aa 122. We previously found that approximately 50% of human MBP(111-129) (MBP122Arg)-specific T cell clones, including MS2-3C8 can proliferate in response to mouse MBP(111-129) (MBP122Lys). However, the other half of T cell clones, including HD4-1C2, cannot proliferate in response to MBP(111-129) (MBP122Lys). We found that MBP(111-129) (MBP122Lys) 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 MBP(111-129) 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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Fatores de Transcrição
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Receptores de Antígenos de Linfócitos T
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Linfócitos T CD4-Positivos
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Antígenos HLA-DR
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Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Esclerose Múltipla
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Proteínas do Tecido Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article