T cell receptor-independent CD2 signal transduction in FcR+ cells - PubMed (original) (raw)

T cell receptor-independent CD2 signal transduction in FcR+ cells

A R Arulanandam et al. J Exp Med. 1991.

Abstract

CD2 subserves both adhesion and signal transduction functions in T cells, thymocytes, and natural killer (NK) cells. In mature T lymphocytes, CD2-mediated signaling function apparently requires surface expression of T cell receptors (TCRs). In contrast, in CD2+ CD3- NK cells and thymocytes, signal transduction through CD2 is TCR independent. To resolve this paradox and characterize TCR-independent triggering mechanisms, we transfected a human CD2 cDNA into a murine mast cell line, C1.MC/57 (Fc epsilon RI+, Fc gamma RII+, Fc gamma RIII+), which is known to produce interleukin 6 (IL-6) as well as release histamine in response to crosslinking of Fc epsilon RI. In the CD2 transfectant, a combination of anti-T11(2) + anti-T11(3) monoclonal antibodies (mAbs) induced a rise in intracellular free calcium [( Ca2+]i), IL-6 production, and histamine release. As expected, no activation was mediated by the same mAbs in C1.MC/57. F(ab)'s fragments of the activatory combination of anti-T11(2) + anti-T11(3) mAbs induced IL-6 in the CD2-transfected mast cells, demonstrating an Fc gamma receptor ectodomain-independent triggering mechanism. In addition, either intact anti-T11(2) or anti-T11(3) IgG alone, which failed to induce [Ca2+]i mobilization in the transfectant, was able to induce IL-6 production. A mAb directed against both Fc gamma RII (previously denoted as Fc gamma RIIb) and Fc gamma RIII (previously denoted as Fc gamma RIIa) inhibits this induction. These results indicate that: (a) Ca2+ mobilization is not essential for IL-6 production; and (b) crosslinking of CD2 and Fc gamma receptors via intact anti-CD2 IgG stimulates IL-6 production. Thus, CD2-mediated IL-6 production occurs by both Fc receptor ectodomain-independent as well as Fc receptor ectodomain-dependent mechanisms in these nonlymphoid cells. Northern blot analysis demonstrates that although the mast cells do not express CD3 zeta or CD3 eta mRNA, they express Fc epsilon RI gamma mRNA. The latter is a known component of Fc gamma RIII as well as Fc epsilon RI, has significant homology to CD3 zeta/eta, and is thought to have a signal transduction function. In these mast cells, CD2 signaling machinery does not require CD3 zeta/eta and may be linked to the Fc epsilon RI gamma subunit. We predict that this subunit or a related structure may confer a TCR-independent signal transduction pathway upon CD2 in CD3- NK cells, thymocytes, and certain B lymphocytes.

PubMed Disclaimer

Cited by

Signals Controlling Lytic Granule Polarization at the Cytotoxic Immune Synapse.
Kabanova A, Zurli V, Baldari CT. Kabanova A, et al. Front Immunol. 2018 Feb 20;9:307. doi: 10.3389/fimmu.2018.00307. eCollection 2018. Front Immunol. 2018. PMID: 29515593 Free PMC article. Review.
Identification of a proline-rich sequence in the CD2 cytoplasmic domain critical for regulation of integrin-mediated adhesion and activation of phosphoinositide 3-kinase.
Kivens WJ, Hunt SW 3rd, Mobley JL, Zell T, Dell CL, Bierer BE, Shimizu Y. Kivens WJ, et al. Mol Cell Biol. 1998 Sep;18(9):5291-307. doi: 10.1128/MCB.18.9.5291. Mol Cell Biol. 1998. PMID: 9710614 Free PMC article.
The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2.
Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB. Bell GM, et al. J Exp Med. 1996 Jan 1;183(1):169-78. doi: 10.1084/jem.183.1.169. J Exp Med. 1996. PMID: 8551220 Free PMC article.
Interaction between human CD2 and CD58 involves the major beta sheet surface of each of their respective adhesion domains.
Arulanandam AR, Kister A, McGregor MJ, Wyss DF, Wagner G, Reinherz EL. Arulanandam AR, et al. J Exp Med. 1994 Nov 1;180(5):1861-71. doi: 10.1084/jem.180.5.1861. J Exp Med. 1994. PMID: 7525842 Free PMC article.
The CD58 (LFA-3) binding site is a localized and highly charged surface area on the AGFCC'C" face of the human CD2 adhesion domain.
Arulanandam AR, Withka JM, Wyss DF, Wagner G, Kister A, Pallai P, Recny MA, Reinherz EL. Arulanandam AR, et al. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11613-7. doi: 10.1073/pnas.90.24.11613. Proc Natl Acad Sci U S A. 1993. PMID: 7505442 Free PMC article.

References

1. Nature. 1989 Oct 26;341(6244):752-4 - PubMed
1. Nature. 1989 May 25;339(6222):312-4 - PubMed
1. J Immunol. 1989 Dec 1;143(11):3787-91 - PubMed
1. Nature. 1989 Sep 14;341(6238):159-62 - PubMed
1. Nature. 1989 Jan 12;337(6203):187-9 - PubMed

T cell receptor-independent CD2 signal transduction in FcR+ cells - PubMed (original) (raw)