CD4/major histocompatibility complex class II interaction analyzed with CD4‐and lymphocyte activation gene‐3 (LAG‐3)‐Ig fusion proteins

B Huard, P Prigent, M Tournier… - European journal of …, 1995 - Wiley Online Library
B Huard, P Prigent, M Tournier, D Bruniquel, F Triebel
European journal of immunology, 1995Wiley Online Library
We analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4
and lymphocyte activation gene (LAG)‐3 recombinant fusion proteins termed CD4Ig and
LAG‐3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when
used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited
by anti‐CD4 and anti‐MHC class II mAb. LAG‐3Ig bound MHC class II molecules with
intermediate avidity (Kd= 60 nM at 37° C). Using LAG‐3Ig as a competitor in a CD4/MHC …
Abstract
We analyzed CD4 major histocompatibility complex (MHC) class II interactions with CD4 and lymphocyte activation gene (LAG)‐3 recombinant fusion proteins termed CD4Ig and LAG‐3Ig. CD4Ig bound MHC class II molecules expressed on the cell surface only when used in the micromolar range. This weak CD4Ig binding was specific, since it was inhibited by anti‐CD4 and anti‐MHC class II mAb. LAG‐3Ig bound MHC class II molecules with intermediate avidity (Kd = 60 nM at 37°C). Using LAG‐3Ig as a competitor in a CD4/MHC class II‐dependent cellular adhesion assay, we showed that this recombinant molecule was able to block CD4/MHC class II interaction. In contrast, no inhibition was observed in a CD4/MHC class II‐dependent T cell cytotoxicity assay. Together, these results suggest that co‐engagement of the TcR with CD4 alters the CD4/MHC class II molecular interaction to become insensitive to LAG‐3Ig competition.
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