Influence of MHC class I molecules on T-cell proliferation induced by CD3 or Thy-1 stimulation

N. Amirayan, E. F. Furrie Deleuil, A. Mellor, L. Leserman, P. Machy

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

We have reported that class I- [and lymphocyte function-associated antigen-1 (LFA-1-)] specific monoclonal antibodies (mAb) inhibit anti-CD3-mediated activation of naive T cells. The present study investigated the mechanism of this inhibition. CD28-specific mAb augmented stimulation induced by soluble CD3 mAb, but this costimulation was also inhibited by anti-class I or anti-LFA-1 mAb. However, stimulation of T cells was not inhibited when activated B cells were present. Neither B7-1- nor B7-2-specific blocking mAb or soluble CTLA-4, CD40 or gp39 restored the inhibition. Thus, other molecules expressed on activated B cells are implicated far T-cell activation, which could compensate blockade of class I or LFA-1 molecules. Inhibition induced by class I-specific mAb could potentially be mediated through extracellular, transmembrane or cytoplasmic domains of the target molecules. These possibilities were evaluated by the use of mice transgenic for the Qa-2 molecule, selected for expression of Qa-2 at levels equivalent to classical class I molecules. Qa-2 is inserted in the membrane through phosphatidylinositol linkages. Antibodies directed to Qa-2 inhibited CD3-induced stimulation, demonstrating that cytoplasmic and transmembrane protein sequences of class I molecules are not necessary for the inhibitory effect. Inhibition thus presumably depends on extracellular domains. Finally, T cells from β2- microglobulin knock-out mice responded to CD3-specific mAb as well as their class I-positive littermates. Nevertheless, stimulation of T cells from these mice with mitogenic anti-Thy-1 mAb was markedly reduced. Signalling by Thy-1 and the CD3 complex may normally occur through pathways in which class I molecules are implicated.

Original languageEnglish (US)
Pages (from-to)71-78
Number of pages8
JournalImmunology
Volume86
Issue number1
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Amirayan, N., Furrie Deleuil, E. F., Mellor, A., Leserman, L., & Machy, P. (1995). Influence of MHC class I molecules on T-cell proliferation induced by CD3 or Thy-1 stimulation. Immunology, 86(1), 71-78.