Journal
IMMUNITY
Volume 16, Issue 4, Pages 521-534Publisher
CELL PRESS
DOI: 10.1016/S1074-7613(02)00301-1
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Funding
- NIDA NIH HHS [R03 DA 14036] Funding Source: Medline
- NIDDK NIH HHS [R21 DK 61329] Funding Source: Medline
- NIGMS NIH HHS [R01 GM 39476, R01 GM 48002] Funding Source: Medline
- NIMH NIH HHS [P30 MH 62261] Funding Source: Medline
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The diverse effects of TCR agonists and antagonists on T cell activation are believed to be modified by the differential recruitment of CD4 or CD8 coreceptors to the TCR-MHCp complex. We used three-dimensional live cell imaging of fluorescence resonance energy transfer (FRET) between CD3zeta and CD4 fused to variants of the green fluorescent protein to investigate TCR-CD4 interactions during T cell activation, We demonstrate that recognition of agonist MHCp complexes triggers intermolecular interaction between CD4 and TCR, detectable across the T-hybridoma-APC contact area. This interaction is blocked by the presence of antagonist ligands without decreasing the recruitment of and CD4 or preventing their partial colocalization in the immunological synapse.
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