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J. Exp. Med.,
Volume 188, Number 9, November 2, 1998 1633-1640
By
From the * Department of Oncology and The interaction of the T cell receptor (TCR) with its cognate peptide-major histocompatibility complex (MHC) on the surface of antigen presenting cells (APCs) is a primary event during
T cell activation. Here we used a dimeric IEk-MCC molecule to study its capacity to activate
antigen-specific T cells and to directly analyze the role of CD4 in physically stabilizing the
TCR-MHC interaction. Dimeric IEk-MCC stably binds to specific T cells. In addition, immobilized dimeric IEk-MCC can induce TCR downregulation and activate antigen-specific T
cells more efficiently than anti-CD3. The potency of the dimeric IEk-MCC is significantly enhanced in the presence of CD4. However, CD4 does not play any significant role in stabilizing
peptide-MHC-TCR interactions as it fails to enhance binding of IEk-MCC to specific T cells
or influence peptide-MHC-TCR dissociation rate or TCR downregulation. Moreover, these
results indicate that dimerization of peptide-MHC class II using an IgG molecular scaffold significantly increases its binding avidity leading to an enhancement of its stimulatory capacity
while maintaining the physiological properties of cognate peptide-MHC complex. These peptide-MHC-IgG chimeras may, therefore, provide a novel approach to modulate antigen-specific T cell responses both in vitro and in vivo.
Department of Pathology, Johns Hopkins University School
of Medicine, Baltimore, Maryland 21205
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