TCR Signaling

The T-Cell Receptor is a protein complex on the surface of T-cell responsible for antigen recognition. The activation induces a number of signaling cascades finally leading to the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines.

Src-family kinases (SFKs1 ) Lck and Fyn phosphorylate TCR ITAMs (immunoreceptor tyrosine-based activation motifs) in the CD3, creating a docking site for ZAP-70. Phosphorylation and activation is modulated by CD45 receptor2 . Zap-70 binds to CD3 zeta chain which positions the protein kinase to phosphorylate the transmembrane protein linker of activated T cells (LAT).

Signaling proteins like SLP-76 can now dock to LAT and gets phosporylated by ZAP-70 as well3. SLP-76 promotes recruitment of Vav (GEF), the adaptor proteins NCK and GADS, and an inducible T cell kinase (Itk). Ltk enables PLCγ1 by phosphorylation which leads to hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce the second messengers diacylglycerol (DAG) and inositol trisphosphate (IP3).

Phosphorylation of phospholipase C γ1 (PLCγ1) by Itk results in the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce the second messenger inositol trisphosphate (IP3) and DAG. DAG activates PKC4 and the MAPK/Erk pathways cascade which leads to activation of transcription factor NF-κB and ATF2 activation and relocation into nucleolus. IP3 promotes release of Ca2+ from the ER, which triggers entry of extracellular Ca2+ into cells through calcium release-activated Ca2+ (CRAC) channels. Calcium-bound calmodulin (Ca2+/CaM) activates the phosphatase calcineurin. Transcription factor NFAT gets activated and promotes IL-2 gene transcription.

The signal cascades are regulated on several occasions to diversify the cell answer. Extracellular signals are recognized by additional cell surface receptors like CD28 or LFA-1 and further regulate cellular response.


  1. Braiman, A and Isakov, N (2015): "The Role of Crk Adaptor Proteins in T-Cell Adhesion and Migration”. Front. Immunol., v.6,2015. [PMID: 4593252]
  2. Courtney, AH (2017): “A Phosphosite within the SH2 Domain of Lck Regulates Its Activation by CD45. ”. Mol Cell , 3;67(3):498-511 [PMID: 28735895]
  3. Wang HY (2001): “Cbl promotes ubiquitination of the T cell receptor zeta through an adaptor function of Zap-70.” J Biol Chem, 276(28):26004-11. [PMID: 11353765]
  4. Lio Y (1999): “Protein kinase C activation inhibits tyrosine phosphorylation of Cbl and its recruitment of Src homology 2 domain-containing proteins.” J Immunol, 162(12):7095-101 [PMID: 10358153]


Antigens in this category:
PDPK1 (3-phosphoinositide Dependent Protein Kinase-1): PDPK1 antibodies PDPK1 ELISA Kits PDPK1 Proteins
ATF2 (Activating Transcription Factor 2): ATF2 antibodies ATF2 ELISA Kits ATF2 Proteins
BCL10 (B-Cell CLL/lymphoma 10): BCL10 antibodies BCL10 ELISA Kits BCL10 Proteins
CCR5 (C-C Chemokine Receptor Type 5): CCR5 antibodies CCR5 ELISA Kits CCR5 Proteins
CREB1 (CAMP Responsive Element Binding Protein 1): CREB1 antibodies CREB1 ELISA Kits CREB1 Proteins
CBL (Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence): CBL antibodies CBL ELISA Kits CBL Proteins
CARD11 (Caspase Recruitment Domain Family, Member 11): CARD11 antibodies CARD11 ELISA Kits CARD11 Proteins
CD247 (CD247 Molecule): CD247 antibodies CD247 ELISA Kits CD247 Proteins
CD28 (CD28): CD28 antibodies CD28 ELISA Kits CD28 Proteins
CD3G (CD3 Antigen, gamma Polypeptide): CD3G antibodies CD3G ELISA Kits CD3G Proteins
CD3D (CD3d Molecule, delta (CD3-TCR Complex)): CD3D antibodies CD3D ELISA Kits CD3D Proteins
CD3E (CD3e Molecule, epsilon (CD3-TCR Complex)): CD3E antibodies CD3E ELISA Kits CD3E Proteins
CD3G (CD3g Molecule, gamma (CD3-TCR Complex)): CD3G antibodies CD3G ELISA Kits CD3G Proteins
CD4 (CD4 Molecule): CD4 antibodies CD4 ELISA Kits CD4 Proteins
CD8A (CD8 Antigen, alpha Polypeptide): CD8A antibodies    
CD80 (CD80): CD80 antibodies CD80 ELISA Kits CD80 Proteins
CD83 (CD83): CD83 antibodies CD83 ELISA Kits CD83 Proteins
CD8A - CD8: CD8A antibodies CD8A ELISA Kits CD8A Proteins
CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)): CDC42 antibodies CDC42 ELISA Kits CDC42 Proteins
CCR5 (Chemokine (C-C Motif) Receptor 5): CCR5 antibodies CCR5 ELISA Kits  
CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase): CHUK antibodies CHUK ELISA Kits CHUK Proteins
DBNL (Drebrin-Like): DBNL antibodies DBNL ELISA Kits DBNL Proteins


Antigens in this category:
FAS (Fas (TNF Receptor Superfamily, Member 6)): FAS antibodies FAS ELISA Kits FAS Proteins
FYN (FYN Oncogene Related To SRC, FGR, YES): FYN antibodies FYN ELISA Kits FYN Proteins
FYB (FYN-Binding Protein): FYB antibodies FYB ELISA Kits FYB Proteins
GATA3 (GATA Binding Protein 3): GATA3 antibodies GATA3 ELISA Kits GATA3 Proteins
GAB2 (GRB2-Associated Binding Protein 2): GAB2 antibodies GAB2 ELISA Kits GAB2 Proteins
GRAP2 (GRB2-Related Adaptor Protein 2): GRAP2 antibodies GRAP2 ELISA Kits GRAP2 Proteins
GRB2 (Growth Factor Receptor-Bound Protein 2): GRB2 antibodies GRB2 ELISA Kits GRB2 Proteins
HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog): HRAS antibodies HRAS ELISA Kits HRAS Proteins


Antigens in this category:
ITK (IL2-Inducible T-Cell Kinase): ITK antibodies ITK ELISA Kits ITK Proteins
ICOS (Inducible T-Cell Co-Stimulator): ICOS antibodies ICOS ELISA Kits ICOS Proteins
IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta): IKBKB antibodies IKBKB ELISA Kits IKBKB Proteins
IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma): IKBKG antibodies IKBKG ELISA Kits IKBKG Proteins
ITPR1 (Inositol 1,4,5-Trisphosphate Receptor, Type 1): ITPR1 antibodies ITPR1 ELISA Kits ITPR1 Proteins
IRF4 (Interferon Regulatory Factor 4): IRF4 antibodies IRF4 ELISA Kits IRF4 Proteins
IL1A (Interleukin 1 alpha): IL1A antibodies IL1A ELISA Kits IL1A Proteins
IL1B (Interleukin 1, beta): IL1B antibodies IL1B ELISA Kits IL1B Proteins
IL15RA (Interleukin 15 Receptor, alpha): IL15RA antibodies IL15RA ELISA Kits IL15RA Proteins
IL17A (Interleukin 17A): IL17A antibodies IL17A ELISA Kits IL17A Proteins
IL9 (Interleukin 9): IL9 antibodies IL9 ELISA Kits IL9 Proteins
JUN - C-JUN: JUN antibodies JUN ELISA Kits JUN Proteins
LAT (Linker For Activation of T Cells): LAT antibodies LAT ELISA Kits LAT Proteins
LHB (Luteinizing Hormone beta Polypeptide): LHB antibodies LHB ELISA Kits LHB Proteins


Antigens in this category:
p38 (MAP kinase p38): p38 antibodies p38 ELISA Kits  
MAPK1 - ERK2: MAPK1 antibodies MAPK1 ELISA Kits MAPK1 Proteins
MAPK14 (Mitogen-Activated Protein Kinase 14): MAPK14 antibodies MAPK14 ELISA Kits MAPK14 Proteins
MAPK3 (Mitogen-Activated Protein Kinase 3): MAPK3 antibodies MAPK3 ELISA Kits MAPK3 Proteins
MAPK8 - JNK: MAPK8 antibodies MAPK8 ELISA Kits MAPK8 Proteins
MAPK9 (Mitogen-Activated Protein Kinase 9): MAPK9 antibodies MAPK9 ELISA Kits MAPK9 Proteins
MAP2K1 (Mitogen-Activated Protein Kinase Kinase 1): MAP2K1 antibodies MAP2K1 ELISA Kits MAP2K1 Proteins
MAP2K2 (Mitogen-Activated Protein Kinase Kinase 2): MAP2K2 antibodies MAP2K2 ELISA Kits MAP2K2 Proteins
MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14): MAP3K14 antibodies MAP3K14 ELISA Kits MAP3K14 Proteins
MAP3K7 (Mitogen-Activated Protein Kinase Kinase Kinase 7): MAP3K7 antibodies MAP3K7 ELISA Kits MAP3K7 Proteins
MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8): MAP3K8 antibodies MAP3K8 ELISA Kits MAP3K8 Proteins
MAP4K1 (Mitogen-Activated Protein Kinase Kinase Kinase Kinase 1): MAP4K1 antibodies   MAP4K1 Proteins
MALT1 (Mucosa Associated Lymphoid Tissue Lymphoma Translocation Gene 1): MALT1 antibodies MALT1 ELISA Kits MALT1 Proteins
NCK1 - Cytoplasmic Protein NCK1: NCK1 antibodies NCK1 ELISA Kits NCK1 Proteins
NFATC1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 1): NFATC1 antibodies NFATC1 ELISA Kits NFATC1 Proteins
NFAT1 (Nuclear Factor of Activated T-Cells, Cytoplasmic, Calcineurin-Dependent 2): NFAT1 antibodies NFAT1 ELISA Kits NFAT1 Proteins
NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1): NFKB1 antibodies NFKB1 ELISA Kits NFKB1 Proteins
NFKBIA (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, alpha): NFKBIA antibodies NFKBIA ELISA Kits NFKBIA Proteins
NFkBP65 - p65: NFkBP65 antibodies NFkBP65 ELISA Kits NFkBP65 Proteins
OPRm - Mu Opioid Receptor: OPRm antibodies    
OPRM1 - Mu Opioid Receptor 1: OPRM1 antibodies OPRM1 ELISA Kits OPRM1 Proteins
PAK1 (P21-Activated Kinase 1): PAK1 antibodies PAK1 ELISA Kits PAK1 Proteins
PLCG1 - Phospholipase C gamma 1: PLCG1 antibodies PLCG1 ELISA Kits PLCG1 Proteins
PSTPIP1 (Proline-serine-threonine Phosphatase Interacting Protein 1): PSTPIP1 antibodies PSTPIP1 ELISA Kits PSTPIP1 Proteins
PKB (Protein Kinase B): PKB antibodies PKB ELISA Kits  
PKCd - PKC delta: PKCd antibodies PKCd ELISA Kits PKCd Proteins
PRKCQ - PKC theta: PRKCQ antibodies PRKCQ ELISA Kits PRKCQ Proteins
PTPN11 (Protein tyrosine Phosphatase, Non-Receptor Type 11): PTPN11 antibodies PTPN11 ELISA Kits PTPN11 Proteins
PTK2B (PTK2B Protein tyrosine Kinase 2 beta): PTK2B antibodies PTK2B ELISA Kits PTK2B Proteins


Antigens in this category:
RIPK2 (Receptor-Interacting Serine-threonine Kinase 2): RIPK2 antibodies RIPK2 ELISA Kits RIPK2 Proteins
RIP2 (ROP Interactive Partner 2): RIP2 antibodies    
SH2B3 (SH2B Adaptor Protein 3): SH2B3 antibodies SH2B3 ELISA Kits SH2B3 Proteins
SHC1 (SHC (Src Homology 2 Domain Containing) Transforming Protein 1): SHC1 antibodies SHC1 ELISA Kits SHC1 Proteins
SOS1 (Son of Sevenless Homolog 1 (Drosophila)): SOS1 antibodies SOS1 ELISA Kits SOS1 Proteins
SKAP1 (Src Kinase Associated phosphoprotein 1): SKAP1 antibodies SKAP1 ELISA Kits SKAP1 Proteins
TRAF6 (TNF Receptor-Associated Factor 6): TRAF6 antibodies TRAF6 ELISA Kits TRAF6 Proteins
TGFB1 (Transforming Growth Factor, beta 1): TGFB1 antibodies TGFB1 ELISA Kits TGFB1 Proteins
TNFRSF9 - CD137: TNFRSF9 antibodies TNFRSF9 ELISA Kits TNFRSF9 Proteins


Antigens in this category:
AKT1 - AKT: AKT1 antibodies AKT1 ELISA Kits AKT1 Proteins
CRK - Crk: CRK antibodies CRK ELISA Kits CRK Proteins
CRKL - CrkL: CRKL antibodies CRKL ELISA Kits CRKL Proteins
HRAS (V-Ha-Ras Harvey Rat Sarcoma Viral Oncogene Homolog): HRAS antibodies HRAS ELISA Kits HRAS Proteins
RAF1 (V-Raf-1 Murine Leukemia Viral Oncogene Homolog 1): RAF1 antibodies RAF1 ELISA Kits RAF1 Proteins
VAV1 (Vav 1 Oncogene): VAV1 antibodies VAV1 ELISA Kits VAV1 Proteins
VAV3 (Vav 3 Oncogene): VAV3 antibodies VAV3 ELISA Kits VAV3 Proteins
VIM - Vimentin: VIM antibodies VIM ELISA Kits VIM Proteins
WASL (Wiskott-Aldrich Syndrome-Like): WASL antibodies WASL ELISA Kits WASL Proteins
ZAP70 (zeta-Chain (TCR) Associated Protein Kinase 70kDa): ZAP70 antibodies ZAP70 ELISA Kits ZAP70 Proteins