Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule

被引:143
作者
Galibert, L
Diemer, GS
Liu, Z
Johnson, RS
Smith, JL
Walzer, T
Comeau, MR
Rauch, CT
Wolfson, MF
Sorensen, RA
de Vries, ARV
Branstetter, DG
Koelling, RM
Scholler, J
Fanslow, WC
Baum, PR
Derry, JM
Yan, W
机构
[1] Amgen Inc, Dept Mol Sci, Seattle, WA 98119 USA
[2] Amgen Inc, Dept Prot Sci, Seattle, WA 98119 USA
[3] Amgen Inc, Dept Inflammat, Seattle, WA 98119 USA
[4] Amgen Inc, Dept Oncol, Seattle, WA 98119 USA
[5] Amgen Inc, Dept Pathol, Seattle, WA 98119 USA
关键词
D O I
10.1074/jbc.M502095200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dendritic cells (DCs) are a phenotypically and functionally heterogenous population of leukocytes with distinct subsets serving a different set of specialized immune functions. Here we applied an in vitro whole cell panning approach using antibody phage display technology to identify cell-surface epitopes specifically expressed on human blood BDCA3(+) DCs. A single- chain antibody fragment (anti-1F12 scFv) was isolated that recognizes a conserved surface antigen expressed on both human BDCA3(+) DCs and mouse CD8 alpha(+) DCs. We demonstrate that anti-1F12 scFv binds Nectin-like protein 2 (Necl2, Tslc1, SynCaM, SgIGSF, or Igsf4), an adhesion molecule involved in tumor suppression, synapse formation, and spermatogenesis. Thus, Necl2 defines a specialized subset of DCs in both mouse and human. We further show that Necl2 binds Class-I-restricted T-cell-associated molecule ( CRTAM), a receptor primarily expressed on activated cytotoxic lymphocytes. When present on antigen presenting cells, Necl2 regulates IL-22 expression by activated CD8(+) T-cells. We propose that Necl2/CRTAM molecular pair could regulate a large panel of cell/cell interactions both within and outside of the immune system.
引用
收藏
页码:21955 / 21964
页数:10
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