An anti-CD2 monoclonal antibody that both inhibits and stimulates t cell activation recognizes a subregion of CD2 distinct from known ligand-binding sites

Karen F. Kozarsky, Carlene Tsai, Cynthia M. Bott, Gopal Allada, Lan Lan Li, David A. Fox

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Abstract

The T lymphocyte glycoprotein CD2 appears to have an important role in human T cell development and activation. A novel anti-CD2 monoclonal antibody, designated UMCD2, was shown to block E rosetting, and therefore was defined as recognizing the T111 ligand-binding epitope. Binding of UMCD2 to T cells and thymocytes was blocked by several, but not all, anti-T111 antibodies, suggesting that the T111 eptope consists of more than one subepitope. In functional studies, the combination of UMCD2 plus anti-T113 was mitogenic for T cells; in some individuals, the level of activation was as high as that seen for the combination of anti-T112 plus anti-T113. However, when UMCD2 was added to other stimuli mitogenic for T lymphocytes, such as IL-2 or anti-CD3-Sepharose, it inhibited T cell responses. Although the combination of UMCD2 and anti-T113 induced an increase in cytoplasmic free calcium, the inhibitory activities of UMCD2 were not accompanied by effects on calcium fluxes. A panel of previously characterized CD2 mutants was then analyzed for binding of UMCD2 and other anti-CD2 monoclonals. Surprisingly, UMCD2 bound to all mutants tested, although the other anti-CD2 antibodies with specificity for the ligand-binding region of CD2 each failed to bind to one or more mutants. These data suggest that binding of antibody to a particular CD2 epitope can have opposite effects on the state of T cell activation, depending on the costimulus. Moreover, inhibitory effects mediated through CD2 may use a signaling mechanism distinct from that used in CD2 pathway activation. Of particular interest, the portion of the CD2 ligand-binding region recognized by UMCD2 is distinct from areas of the CD2 molecule that have previously been studied.

Original languageEnglish (US)
Pages (from-to)235-246
Number of pages12
JournalCellular Immunology
Volume150
Issue number2
DOIs
StatePublished - Sep 1993

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ASJC Scopus subject areas

  • Immunology

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