Alterations in CD4-binding regions of the MHC class II molecule I-Ek do not impede CD4+ T cell development.
J Immunol
; 162(3): 1348-58, 1999 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-9973389
ABSTRACT
The T cell coreceptors CD4 and CD8 enhance T cell responses to TCR signals by participating in complexes containing TCR, coreceptor, and MHC molecules. These ternary complexes are also hypothesized to play a seminal role during T cell development, although the precise timing, frequency, and consequences of TCR-coreceptor-MHC interactions during positive selection and lineage commitment remain unclear. To address these issues, we designed transgenic mice expressing mutant I-Ek molecules with reduced CD4-binding capability. These transgenic lines were crossed to three different lines of I-Ek-specific TCR transgenic mice, and the efficiency of production of CD4+ lineage cells in the doubly transgenic progeny was assessed. Surprisingly, replacing wild-type I-Ek molecules with these mutant molecules did not affect the production of CD4+CD8- thymocytes or CD4+ peripheral T cells expressing any of the three TCRs examined. These data, when considered together with other experiments addressing the role of coreceptor during development, suggest that not all MHC class II-specific thymocytes require optimal and simultaneous TCR-CD4-MHC interactions to mature. Alternatively, it is possible that these particular alterations of I-Ek do not disrupt the CD4-MHC interaction adequately, potentially indicating functional differences between I-A and I-E MHC class II molecules.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
/
Antígenos de Histocompatibilidade Classe II
/
Antígenos CD4
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos