Coengagement of CD2 with LFA‐1 or VLA‐4 by bispecific ligand fusion proteins primes T cells to respond more effectively to T cell receptor‐dependent signals

Autor: Dietsch, Mary T., Chan, Po‐Ying, Kanner, Steven B., Gilliland, Lisa K., Ledbetter, Jeffrey A., Linsley, Peter S., Aruffo, Alejandro
Zdroj: Journal of Leukocyte Biology; October 1994, Vol. 56 Issue: 4 p444-452, 9p
Abstrakt: To examine the effects of ligand engagement and accessory molecule juxtaposition on T cell receptor (TCR) signaling, we prepared LFA‐3/ICAM‐1 Rg and LFA‐3/VCAM‐1 Rg bispecific immunoglobulin fusion proteins (Rg, recombinant globulin). These novel fusion proteins allowed us to examine the effects of ligand driven co‐engagement of T cell proteins CD2 and LFA‐1 or CD2 and VLA‐4 on TCR‐dependent mobilization of intracellular Ca2+. We observed that preincubation of resting T cells with LFA‐3/ICAM‐1 Rg or LFA‐3/VCAM‐1 Rg fusion proteins resulted in significantly enhanced mobilization of intracellular Ca2+following TCR‐accessory molecule cross‐linking relative to T cells preincubated with each of the monospecific Rgs alone or with combinations of the monospecific Rg fusion proteins. In addition, such coengagement stimulated TCR‐dependent activation and tyrosine phosphorylation of phospholipase Cγ1 (PLCγ1). These results suggest that when T cells interact with antigen presenting cells the engagement of multiple cell adhesion molecules such as CD2, LFA‐1, and VLA‐4 primes the T cell to respond more effectively to signals delivered through the TCR. J. Leukoc. Biol. 56: 444–452; 1994.
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