CD28 affects the earliest signaling events generated by TCR engagement

Eur J Immunol. 1998 Jul;28(7):2131-42. doi: 10.1002/(SICI)1521-4141(199807)28:07<2131::AID-IMMU2131>3.0.CO;2-Q.

Abstract

The efficiency and magnitude of T cell responses are influenced by ligation of the co-stimulatory receptor CD28 by B7 molecules expressed on antigen-presenting cells (APC). In contrast to most previous studies in which agonistic anti-TCR/CD3 and anti-CD28 antibodies were employed, here we have investigated the contribution of CD28 to T cell activation under physiological conditions of antigen presentation. Jurkat T cells and primary T cells from TCR-transgenic mice stimulated with superantigen and antigen, respectively, presented by B7-expressing APC were utilized. In both systems we show that inhibiting CD28/B7 interaction resulted in impaired TCR-induced tyrosine phosphorylation of the signal-transducing zeta chain and ZAP-70. Consistent with a blockade of TCR-proximal signaling events, Jurkat cells stimulated in the absence of CD28 ligation were found to have strongly diminished tyrosine phosphorylation of cellular substrates and downstream signaling pathways such as Ca2+/calcineurin, ERK/MAPK and JNK. Our results provide evidence for a role of CD28 in enhancing TCR signaling capacity during the earliest stages of T cell:APC interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / physiology
  • CD28 Antigens / physiology*
  • DNA-Binding Proteins / physiology
  • Genes, fos
  • Humans
  • Interleukin-2 / biosynthesis
  • JNK Mitogen-Activated Protein Kinases*
  • Jurkat Cells
  • MAP Kinase Kinase 4
  • Mice
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases / physiology
  • NFATC Transcription Factors
  • Nerve Tissue Proteins / physiology
  • Nuclear Proteins*
  • Protein Kinases / physiology
  • Receptors, Antigen, T-Cell / physiology*
  • Transcription Factor AP-1 / physiology
  • Transcription Factors / physiology

Substances

  • B7-1 Antigen
  • CD28 Antigens
  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factor AP-1
  • Transcription Factors
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases