PMID: 9539765May 16, 1998Paper

Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+) T cells in vivo

Proceedings of the National Academy of Sciences of the United States of America
J M RiberdyC Doyle

Abstract

The experiments presented in this report were designed to specifically examine the role of CD4-major histocompatibility complex (MHC) class II interactions during T cell development in vivo. We have generated transgenic mice expressing class II molecules that cannot interact with CD4 but that are otherwise competent to present peptides to the T cell receptor. MHC class II expression was reconstituted in Abeta gene knock-out mice by injection of a transgenic construct encoding either the wild-type I-Abetab protein or a construct encoding a mutation designed to specifically disrupt binding to the CD4 molecule. We demonstrate that the mutation, EA137 and VA142 in the beta2 domain of I-Ab, is sufficient to disrupt CD4-MHC class II interactions in vivo. Furthermore, we show that this interaction is critical for the efficient selection of a complete repertoire of mature CD4(+) T helper cells as evidenced by drastically reduced numbers of conventional CD4(+) T cells in animals expressing the EA137/VA142 mutant I-Ab and by the failure to positively select the transgenic AND T cell receptor on the mutated I-Ab. These results underscore the importance of the CD4-class II interaction in the development of mature peripheral CD4(+) T cells.

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Nov 9, 2000·Immunology Today·M A Basson, R Zamoyska
Jan 16, 2002·Current Opinion in Immunology·Rolf König
May 30, 2002·Nature Reviews. Immunology·Ronald N Germain
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May 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hye-Jung KimDerek B Sant'Angelo
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Jan 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasuhiro TanakaJianlin Gong
Jun 19, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·John A GebeGerald T Nepom
Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jose-Ignacio Rodriguez-BarbosaMegan Sykes
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Jul 23, 2018·Journal of Experimental & Clinical Cancer Research : CR·Michelle H TownsendKim L O'Neill

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