Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Pubmed ID :25363763
Publication Date : //

CEACAM1 regulates TIM-3-mediated tolerance and exhaustion.


T-cell immunoglobulin domain and mucin domain-3 (TIM-3, also known as HAVCR2) is an activation-induced inhibitory molecule involved in tolerance and shown to induce T-cell exhaustion in chronic viral infection and cancers. Under some conditions, TIM-3 expression has also been shown to be stimulatory. Considering that TIM-3, like cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death 1 (PD-1), is being targeted for cancer immunotherapy, it is important to identify the circumstances under which TIM-3 can inhibit and activate T-cell responses. Here we show that TIM-3 is co-expressed and forms a heterodimer with carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on activated T cells and involved in T-cell inhibition. Biochemical, biophysical and X-ray crystallography studies show that the membrane-distal immunoglobulin-variable (IgV)-like amino-terminal domain of each is crucial to these interactions. The presence of CEACAM1 endows TIM-3 with inhibitory function. CEACAM1 facilitates the maturation and cell surface expression of TIM-3 by forming a heterodimeric interaction in cis through the highly related membrane-distal N-terminal domains of each molecule. CEACAM1 and TIM-3 also bind in trans through their N-terminal domains. Both cis and trans interactions between CEACAM1 and TIM-3 determine the tolerance-inducing function of TIM-3. In a mouse adoptive transfer colitis model, CEACAM1-deficient T cells are hyper-inflammatory with reduced cell surface expression of TIM-3 and regulatory cytokines, and this is restored by T-cell-specific CEACAM1 expression. During chronic viral infection and in a tumour environment, CEACAM1 and TIM-3 mark exhausted T cells. Co-blockade of CEACAM1 and TIM-3 leads to enhancement of anti-tumour immune responses with improved elimination of tumours in mouse colorectal cancer models. Thus, CEACAM1 serves as a heterophilic ligand for TIM-3 that is required for its ability to mediate T-cell inhibition, and this interaction has a crucial role in regulating autoimmunity and anti-tumour immunity.

Authors : Huang Yu-Hwa , Zhu Chen , Kondo Yasuyuki , Anderson Ana C , Gandhi Amit , Russell Andrew , Dougan Stephanie K , Petersen Britt-Sabina , Melum Espen , Pertel Thomas , Clayton Kiera L , Raab Monika , Chen Qiang , Beauchemin Nicole , Yazaki Paul J , Pyzik Michal , Ostrowski Mario A , Glickman Jonathan N , Rudd Christopher E , Ploegh Hidde L , Franke Andre , Petsko Gregory A , Kuchroo Vijay K , Blumberg Richard S ,

Related products :

Catalog number Product name Quantity
30-561 TRAF3IP3 may function as an adapter molecule that regulates TRAF3-mediated JNK activation. 0.05 mg
26-210 LAX1 is a single-pass type III membrane protein. It negatively regulates TCR (T-cell antigen receptor)-mediated signaling in T-cells and BCR (B-cell antigen receptor)-mediated signaling in B-cells. 0.05 mg
28-324 The C_EBP family of transcription factors regulates viral and cellular CCAAT_enhancer element-mediated transcription. C_EBP proteins contain the bZIP region, which is characterized by two motifs in th 0.05 mg
DL-CEACAM1-Hu Human Carcinoembryonic Antigen Related Cell Adhesion Molecule 1 (CEACAM1) ELISA Kit 96T
A1702 CEACAM1 Primary Antibody, CEACAM1, Species: Human Recombinant Protein Source: Rabbit Polyclonal 50ug
LF-MA42484 Anti-CEACAM1 (2F6), Mouse Monoclonal to CEACAM1, Isotype IgG1, Host Mouse 50
29-961 Transport of folate compounds into mammalian cells can occur via receptor-mediated or carrier-mediated mechanisms. A functional coordination between these 2 mechanisms has been proposed to be the meth 0.1 mg
DL-CEACAM1-Hu CEACAM1 ELISA kit 96T
orb83934 Mouse CEACAM1 His tag protein Recombinant Mouse CEACAM1 His tag protein. For research use only. 100
orb82909 Human CEACAM1 His tag protein Recombinant Human CEACAM1 His tag protein. For research use only. 100
28-652 Yaf2 binds to MYC and inhibits MYC-mediated transactivation. Yaf2 also binds to MYCN and enhances MYCN-dependent transcriptional activation. Yaf2 increases calpain 2-mediated proteolysis of YY1 in vit 0.05 mg
4070 Morphine Tolerance Peptide 100mg
4070 Morphine Tolerance Peptide 100mg
4070 Morphine Tolerance Peptide 100mg
050-13 Morphine Tolerance Peptide (Cyclo Leu_Gly) _ 5mg 5 mg
AS09474 AtMTP4 | metal tolerance protein B 100 ul
AS09 474 AtMTP4 | metal tolerance protein B 100 ul
orb93285 Mouse CEACAM1 gene Mouse CEACAM1 gene is a cDNA gene. For research use only. 10
E7554h Human Increased Sodium Tolerance 1 ELISA Kit 96T
PRO-812 Recombinant Human CutA Divalent Cation Tolerance Homolog 5µg
PRO-812 Recombinant Human CutA Divalent Cation Tolerance Homolog 1mg
RPR-812 Recombinant Human CutA Divalent Cation Tolerance Homolog 5
pro-812 Recombinant Human CutA Divalent Cation Tolerance Homolog 1mg
pro-812 Recombinant Human CutA Divalent Cation Tolerance Homolog 25
D-0625 Morphine Tolerance Peptide 98 percent C8H14N2O2 CAS: 5845-67-0 5mg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur | Gentaur





GENTAUR Ltd.
Unicorn House, Station Cl
Hertfordshire, Potters Bar EN6 1TL
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017
RIB 30004 00187 00010092253 10
BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG
IBAN FR76 3000 4001 8700 0100 9225 310
france@gentaur.com | Gentaur | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur | Gentaur