Open AccessDisruption of the CD4–major histocompatibility complex class II interaction blocks the development of CD4+T cellsin vivo
Author(s) -
Janice M. Riberdy,
Elahe A. Mostaghel,
Carolyn A. Doyle
Publication year - 1998
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.95.8.4493
Subject(s) - major histocompatibility complex , biology , t cell , t cell receptor , microbiology and biotechnology , mhc class i , mutation , mhc class ii , genetics , gene , immune system
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 developmentin 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 Aβ gene knock-out mice by injection of a transgenic construct encoding either the wild-type I-Aβb 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 β2 domain of I-Ab , is sufficient to disrupt CD4–MHC class II interactionsin 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.