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.
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 CD8alpha(+) 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.
Galibert
Laurent
L
Department of Molecular Sciences, Amgen Inc., 1201 Amgen Court, Seattle, WA 98119-3105, USA.
Diemer
Geoffrey S
GS
Liu
Zhi
Z
Johnson
Richard S
RS
Smith
Jeffrey L
JL
Walzer
Thierry
T
Comeau
Michael R
MR
Rauch
Charles T
CT
Wolfson
Martin F
MF
Sorensen
Rick A
RA
Van der Vuurst de Vries
Anne-Renée
AR
Branstetter
Daniel G
DG
Koelling
Raymond M
RM
Scholler
John
J
Fanslow
William C
WC
Baum
Peter R
PR
Derry
Jonathan M
JM
Yan
Wei
W
D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007107:Immune System / Q000502:physiology; D015151:Immunoblotting; D007136:Immunoglobulins / Q000378:metabolism* / Q000502:physiology*; D047468:Immunoprecipitation; D007378:Interleukins / Q000096:biosynthesis; D016086:Lentivirus / Q000235:genetics; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017830:Octoxynol / Q000494:pharmacology; D019151:Peptide Library; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D000097043:Interleukin-22
D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D007378:Interleukins; D008024:Ligands; D008565:Membrane Proteins; D017830:Octoxynol; D019151:Peptide Library; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D000097043:Interleukin-22; C498598:Cadm1 protein, mouse; C408522:class-I restricted T cell-associated molecule