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Related Experiment Videos

CD3 and CD2 ligation alters CD49d epitope expression

J Lin1, L Qin, K D Chavin

  • 1Department of Surgery, University of Michigan, Ann Arbor 48109-0331, USA.

Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology
|January 1, 1995
PubMed
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Anti-CD2 and anti-CD3 monoclonal antibodies (mAbs) synergistically enhance allograft survival by inducing tolerance. These mAbs selectively decrease integrin alpha 4 chain epitope expression on T cells, offering a novel mechanism for tolerance induction.

Area of Science:

  • Immunology
  • Cell Biology
  • Transplantation Immunology

Background:

  • The combination of anti-CD2 and anti-CD3 monoclonal antibodies (mAbs) is known to synergistically prolong allograft survival and induce antigen-specific tolerance.
  • Altered expression of cell surface molecules is a potential factor in tolerance induction.

Purpose of the Study:

  • To investigate the effect of anti-CD2 and anti-CD3 mAbs on the expression of adhesion molecules on splenic T cells.
  • To elucidate the role of these mAbs in regulating T cell surface molecule expression for tolerance induction.

Main Methods:

  • In vitro analysis of splenic T cells treated with anti-CD2 and anti-CD3 mAbs.
  • Flow cytometry to assess the expression of integrin alpha 4 chain epitopes (recognized by R1-2 and PS/2 anti-CD49d mAbs), integrin beta 1 and beta 7 chains, and other adhesion molecules (CD11a, CD18, CD44, CD45, CD48, CD54, CD62L).

Related Experiment Videos

  • Investigation of factors influencing R1-2 epitope expression, including cAMP levels, IL-2, other cytokines, and the divalent cation Mn2+.
  • Assessment of functional binding to VCAM-1 and graft survival in a cardiac allograft model.

    • Main Results:

    • Anti-CD2 mAb alone did not affect R1-2 or PS/2 epitope expression. Anti-CD3 mAb decreased R1-2 epitope expression while leaving PS/2 unchanged. The combination further decreased R1-2 expression.
    • Expression of integrin beta 1 and beta 7 chains remained unchanged. Other adhesion molecules (CD11a, CD18, CD44, CD45, CD48, CD54, CD62L) were upregulated by anti-CD2 or anti-CD3 mAbs.
    • Decreased R1-2 epitope expression was anti-CD3 dependent, augmented by anti-CD2, correlated with increased cAMP, and could be prevented by IL-2. R1-2 epitope expression was restored by Mn2+, enhancing VCAM-1 binding.
    • The R1-2 mAb, but not the PS/2 mAb, prolonged cardiac allograft survival.

    Conclusions:

    • Anti-CD2 and anti-CD3 mAbs selectively decrease integrin alpha 4 chain epitope expression on T cells via conformational regulation.
    • This selective decrease in a CD49d epitope is unique compared to the general upregulation of other T-cell adhesion receptors.
    • These findings provide a mechanistic explanation for the synergistic effect of anti-CD2 and anti-CD3 mAbs in promoting tolerance and prolonging allograft survival.