T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density

Int Immunol. 1999 May;11(5):777-86. doi: 10.1093/intimm/11.5.777.

Abstract

CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression is up-regulated upon T cell activation. In order to elucidate a possible role of CD147 in T cell biology, we established 15 specific mAb. Seven distinct epitopes were defined by the mAb panel. Most of the mAb bound only to phytohemagglutinin (PHA)-activated but not resting T cells. We demonstrate that this was not because of true expression of activation-dependent neoepitopes but rather due to bivalent binding of the relatively low-affinity mAb (affinity constant KA values between 2.25 x 10(8) and 7 x 10(9) M-1) to the more densely expressed and/or more clustered CD147 molecules on the activated T cells. In contrast, the mAb with higher affinity (KA > 7 x 10(9) M-1) could stably bind in a monovalent fashion even to the relatively low dense CD147 molecules on resting T cells. This model might more generally explain the nature of 'activation epitopes' described previously in other leukocyte surface molecules. Finally, we provide evidence that induction of ordered dimerization of CD147 by a mAb directed to a unique epitope results in strong inhibition of CD3-mediated T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Affinity*
  • Antigens, CD*
  • Antigens, Neoplasm*
  • Antigens, Surface*
  • Avian Proteins*
  • Basigin
  • Blood Proteins*
  • Epitope Mapping
  • Humans
  • Lymphocyte Activation*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Neoplasm
  • Antigens, Surface
  • Avian Proteins
  • BSG protein, human
  • Blood Proteins
  • Bsg protein, Gallus gallus
  • Bsg protein, mouse
  • Bsg protein, rat
  • Membrane Glycoproteins
  • Basigin