ILDR2 Is a Novel B7-like Protein That Negatively Regulates T Cell Responses

J Immunol. 2018 Mar 15;200(6):2025-2037. doi: 10.4049/jimmunol.1700325.

Iris Hecht ¹, Amir Toporik ², Joseph R Podojil ³ ⁴, Ilan Vaknin ², Gady Cojocaru ², Anat Oren ², Elizabeta Aizman ², Spencer C Liang ⁵, Ling Leung ⁵, Yosef Dicken ², Amit Novik ², Nadav Marbach-Bar ², Aziza Elmesmari ⁶, Clare Tange ⁶, Ashley Gilmour ⁶, Donna McIntyre ⁶, Mariola Kurowska-Stolarska ⁶, Kay McNamee ⁷, Judith Leitner ⁸, Shirley Greenwald ², Liat Dassa ², Zurit Levine ², Peter Steinberger ⁸, Richard O Williams ⁷, Stephen D Miller ³ ⁴, Iain B McInnes ⁶, Eyal Neria ², Galit Rotman ²

Affiliations

1 Compugen Ltd., Holon 5885849, Israel; Irish@cgen.com.
2 Compugen Ltd., Holon 5885849, Israel.
3 Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
4 Interdepartmental Immunobiology Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
5 Compugen USA Inc., South San Francisco, CA 94080.
6 Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, United Kingdom.
7 Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford OX3 7FY, United Kingdom; and.
8 Division of Immune Receptors and T Cell Activation, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria.

PMID: 29431694 DOI: 10.4049/jimmunol.1700325

Abstract

The B7-like protein family members play critical immunomodulatory roles and constitute attractive targets for the development of novel therapies for human diseases. We identified Ig-like domain-containing receptor (ILDR)2 as a novel B7-like protein with robust T cell inhibitory activity, expressed in immune cells and in immune-privileged and inflamed tissues. A fusion protein, consisting of ILDR2 extracellular domain with an Fc fragment, that binds to a putative counterpart on activated T cells showed a beneficial effect in the collagen-induced arthritis model and abrogated the production of proinflammatory cytokines and chemokines in autologous synovial-like cocultures of macrophages and cytokine-stimulated T cells. Collectively, these findings point to ILDR2 as a novel negative regulator for T cells, with potential roles in the development of immune-related diseases, including autoimmunity and Cancer.

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