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The protein interactions of the immunoglobulin receptor family tyrosine‐based activation motifs present in the T cell receptor ζ subunits and the CD3 γ,δ and ϵ chains

1996; Wiley; Volume: 26; Issue: 5 Linguagem: Inglês

10.1002/eji.1830260516

1521-4141

Narin Osman, Helen Turner, S C Lucas, Karin Reif, Doreen A. Cantrell,

Monoclonal and Polyclonal Antibodies Research

Abstract Immunoglobulin family tyrosine‐based activation motifs (ITAM), which define the conserved signaling sequence EX 2 YX 2 L/IX 7 YX 2 L/I, couple the T cell antigen receptor (TCR) to cellular proteins including protein tyrosine kinases (PTK) and adapter molecules. The TCR is a multichain complex with four invariant chains CD3γ, δ and ϵ that each contain a single ITAM and the TCR ζ chain that contains three ITAM. The present study explores the protein interactions of the doubly phosphorylated CD3 γ, δ, ϵ ITAM to determine whether they have common or unique biochemical properties. The data show that the doubly phosphorylated ITAM all bind the PTK ZAP‐70, but the ITAM also variably bind the PTK p59fyn and the adapters Shc, Grb‐2 and the p85 regulatory subunit of phosphoinositol 3′ kinase. The CD3 and ζ ITAM display a hierarchy of ZAP‐70 binding: ζ1 = γ = δ > ζ3 > ζ2 = ϵ. Shc, Grb‐2 and p85 could bind the ζ ITAM and the CD3 γ and δ ITAM, but not the CD3 ϵ ITAM. There were also subtle differences in the hierarchy of reactivity of these adapters for the CD3 γ,δ and ζ ITAM that show that the ζ, CD3 γ, δ and ϵ ITAM have different binding properties. The present study thus shows that the different ITAM of the TCR/CD3 complex can interact with different cytosolic effectors, indicating that differential ITAM phosphorylation during T cell activation could be a mechanism to generate signaling diversity by the TCR complex.