CD28 affects the earliest signaling events generated by TCR engagement.

Journal article

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.

Authors: Tuosto, L; Acuto, O

• Publication status: Published
• Journal: European journal of immunology
• Volume: 28
• Issue: 7
• Pages: 2131-2142
• Publication date: 1998-07-01
• DOI: 10.1002/(sici)1521-4141(199807)28:07<2131::aid-immu2131>3.0.co;2-q
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: NFATC Transcription Factors; Jurkat Cells; Humans; Mitogen-Activated Protein Kinase Kinases; Transcription Factors; Mice; Animals; Interleukin-2; Transcription Factor AP-1; JNK Mitogen-Activated Protein Kinases; DNA-Binding Proteins; Antigens, CD80; Antigens, CD28; Mitogen-Activated Protein Kinases; Receptors, Antigen, T-Cell; Nuclear Proteins; MAP Kinase Kinase 4; Protein Kinases; Nerve Tissue Proteins; Genes, fos