Display Settings:

Format

Send to:

Choose Destination
J Immunol. 2008 Dec 1;181(11):7639-48.

Signals and sequences that control CD28 localization to the central region of the immunological synapse.

Author information

  • 1The David H Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA.

Abstract

During T cell interaction with APC, CD28 is recruited to the central region (cSMAC) of the immunological synapse. CD28-mediated signaling through PI3K results in the recruitment of protein kinase C-theta (PKCtheta) to the cSMAC, activation of NF-kappaB, and up-regulation of IL-2 transcription. However, the mechanism that mediates CD28 localization to the cSMAC and the functional consequences of CD28 localization to the cSMAC are not understood. In this report, we show that CD28 recruitment and persistence at the immunological synapse requires TCR signals and CD80 engagement. Addition of mAb to either MHC class II or CD80 results in the rapid displacement of CD28 from the immunological synapse. Ligand binding is not sufficient for CD28 localization to the immunological synapse, as truncation of the cytosolic tail of CD28 disrupts synapse localization without effecting the ability of CD28 to bind CD80. Furthermore, a single point mutation in the CD28 cytosolic tail (tyrosine 188) interferes with the ability of CD28 to preferentially accumulate at the cSMAC. PKCtheta distribution at the immunological synapse mirrors the distribution of tyrosine 188-mutated CD28, indicating that CD28 drives the localization of PKCtheta even when CD28 is not localized to the cSMAC. Mutation of tyrosine 188 also results in diminished activation of NF-kappaB, suggesting that CD28-mediated localization of PKCtheta to the cSMAC is important for efficient signal transduction. These data reinforce the importance of the interplay of signals between TCR and CD28 and suggest that CD28 signaling through PCKtheta may be mediated through localization to the cSMAC region of the immunological synapse.

PMID:
19017952
[PubMed - indexed for MEDLINE]
PMCID:
PMC3993010
Free PMC Article

Images from this publication.See all images (8)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Publication Types, MeSH Terms, Substances, Grant Support

Publication Types

MeSH Terms

Substances

Grant Support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk