Collaboration of TCR-, CD4- and CD28-mediated signalling in antigen-specific MHC class II-restricted T-cells

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Abstract

A previously developed experimental system was applied to obtain qualitative and quantitative data on the contribution of TCR-, CD4- and CD28-mediated signalling in the activation of an antigen specific T-cell hybridoma. All the three signal transducing receptors were stimulated by their natural ligands, and intermediate and late responses of an I-E(d) restricted, CD4+, influenza HA specific murine T-hybridoma (IP-12-7) were monitored by measuring the concentration of intracellular calcium [Ca2+](i) and secreted IL-2. This type of analysis of T-cell activation revealed: (i) calcium mobilization induced by peptide loaded APC requires rapid conjugate formation; (ii) a direct correlation between the magnitude of the intermediate and the late responses was observed as a consequence of differential TCR ligation modulated by peptide dose or by the presence CD4; (iii) considering the APC/peptide and T/APC ratios, the concentration dependence of the intermediate and late responses was similar in both assays but a substantial difference in the sensitivity of the two methods was observed; (iv) CD4 mediated signalling has a co-stimulatory effect predominantly at suboptimal in vitro conditions; and (v) sustained increase of [Ca2+](i) as well as the production of high concentrations of IL-2 is highly dependent on the CD28-B7 interaction. These results demonstrate that distinct peptide doses and the presence or absence of CD4 result in quantitative changes in T-cell responses, while the degree of CD28 mediated signalling has a qualitative affect on the outcome of T-cell activation, revealed by complete or partial inhibition of IL-2 secretion as a result of limited CD28-B7 interaction as well as by alteration in the duration and time kinetics of the calcium response.

Original languageEnglish
Pages (from-to)135-144
Number of pages10
JournalImmunology letters
Volume54
Issue number2-3
DOIs
Publication statusPublished - Dec 2 1996

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Keywords

  • MHC class II-restricted T-cells
  • TCR-, CD4- and CD28-mediated signalling
  • antigen specific T-cell hybridoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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