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Publication Abstract from PubMed

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint protein that inhibits the T cell response against cancer. Similar to PD-1 and CTLA-4, a blockade of VISTA promotes tumor clearance by the immune system. Here, we report a 1.85 A crystal structure of the elusive human VISTA extracellular domain, whose lack of homology necessitated a combinatorial MR-Rosetta approach for structure determination. We highlight features that make the VISTA immunoglobulin variable (IgV)-like fold unique among B7 family members, including two additional disulfide bonds and an extended loop region with an attached helix that we show forms a contiguous binding epitope for a clinically relevant anti-VISTA antibody. We propose an overlap of this antibody-binding region with the binding epitope for V-set and Ig domain containing 3 (VSIG3), a purported functional binding partner of VISTA. The structure and functional epitope presented here will help guide future drug development efforts against this important checkpoint target.

Structure and Functional Binding Epitope of V-domain Ig Suppressor of T Cell Activation.,Mehta N, Maddineni S, Mathews II, Andres Parra Sperberg R, Huang PS, Cochran JR Cell Rep. 2019 Sep 3;28(10):2509-2516.e5. doi: 10.1016/j.celrep.2019.07.073. PMID:31484064^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.