Disruption of CD8-dependent negative and positive selection of thymocytes is correlated with a decreased association between CD8 and the protein tyrosine kinase, p56lck

Nicolai S C Van Oers, Alex M. Garvin, Craig B. Davis, Katherine A. Forbush, Douglas A. Carlow, Dan R. Littman, Roger M. Perlmutter, Hung Sia Teh

Research output: Contribution to journalArticle

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Abstract

The CD4 and CD8 coreceptor molecules on immature thymocytes participate in T cell repertoire selection.To examine more definitively the role of CD4 and CD8 in the negative and positive selection of immature thymocytes, we generated transgenic mice with elevated surface CD4 expression and mated them with mice expressing a transgenicT cell receptor. Augmented CD4 expression was found to markedly alter CD8-dependent negative and positive selection of T cells specific for the male (H-Y) antigen presented by H-2Db major histocompatibility complex class I molecules. Moreover, the cytoplasmic tail of CD4 was essential for effecting these alterations, since the overexpression of tailless CD4 molecules failed to influence the outcome of CD8-dependent selection. The inhibition of positive and negative selection in double-transgenic mice expressing the full-length CD4 molecule was associated with a decreased interaction between the protein tyrosine kinase p56lck and CD8. These results strongly implicate p56lck in T cell repertoire selection.

Original languageEnglish (US)
Pages (from-to)735-743
Number of pages9
JournalEuropean Journal of Immunology
Volume22
Issue number3
StatePublished - Mar 1992

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Thymocytes
Protein-Tyrosine Kinases
CD4 Antigens
T-Lymphocytes
Transgenic Mice
H-Y Antigen
Major Histocompatibility Complex
Tail

ASJC Scopus subject areas

  • Immunology

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Disruption of CD8-dependent negative and positive selection of thymocytes is correlated with a decreased association between CD8 and the protein tyrosine kinase, p56lck . / Van Oers, Nicolai S C; Garvin, Alex M.; Davis, Craig B.; Forbush, Katherine A.; Carlow, Douglas A.; Littman, Dan R.; Perlmutter, Roger M.; Teh, Hung Sia.

In: European Journal of Immunology, Vol. 22, No. 3, 03.1992, p. 735-743.

Research output: Contribution to journalArticle

Van Oers, Nicolai S C ; Garvin, Alex M. ; Davis, Craig B. ; Forbush, Katherine A. ; Carlow, Douglas A. ; Littman, Dan R. ; Perlmutter, Roger M. ; Teh, Hung Sia. / Disruption of CD8-dependent negative and positive selection of thymocytes is correlated with a decreased association between CD8 and the protein tyrosine kinase, p56lck In: European Journal of Immunology. 1992 ; Vol. 22, No. 3. pp. 735-743.
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abstract = "The CD4 and CD8 coreceptor molecules on immature thymocytes participate in T cell repertoire selection.To examine more definitively the role of CD4 and CD8 in the negative and positive selection of immature thymocytes, we generated transgenic mice with elevated surface CD4 expression and mated them with mice expressing a transgenicT cell receptor. Augmented CD4 expression was found to markedly alter CD8-dependent negative and positive selection of T cells specific for the male (H-Y) antigen presented by H-2Db major histocompatibility complex class I molecules. Moreover, the cytoplasmic tail of CD4 was essential for effecting these alterations, since the overexpression of tailless CD4 molecules failed to influence the outcome of CD8-dependent selection. The inhibition of positive and negative selection in double-transgenic mice expressing the full-length CD4 molecule was associated with a decreased interaction between the protein tyrosine kinase p56lck and CD8. These results strongly implicate p56lck in T cell repertoire selection.",
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AU - Davis, Craig B.

AU - Forbush, Katherine A.

AU - Carlow, Douglas A.

AU - Littman, Dan R.

AU - Perlmutter, Roger M.

AU - Teh, Hung Sia

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