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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
Author(s) -
Dietsch Mary T.,
Chan PoYing,
Kanner Steven B.,
Gilliland Lisa K.,
Ledbetter Jeffrey A.,
Linsley Peter S.,
Aruffo Alejandro
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.56.4.444
Subject(s) - t cell receptor , biology , fusion protein , t cell , microbiology and biotechnology , receptor , recombinant dna , biochemistry , immunology , immune system , gene
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 Ca 2+ . 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 Ca 2+ 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 C γ 1 (PLC γ 1). 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.