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.


References:

  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]


Receptor and Membran Proteins

CD28 (CD28):

The protein encoded by this gene is essential for T-cell proliferation and survival, cytokine production, and T-helper type-2 development. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2011].   More...

CD4 (CD4 Molecule):

TRAT1 - T Cell Receptor Associated Transmembrane Adaptor 1

Antigens in this category:
B2M - beta-2 Microglobulin: B2M antibodies B2M ELISA Kits B2M Proteins
CD247 (CD247 Molecule): CD247 antibodies CD247 ELISA Kits CD247 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
CD3D (CD3d Molecule, delta (CD3-TCR Complex)): CD3D antibodies CD3D ELISA Kits CD3D Proteins
CD8A (CD8 Antigen, alpha Polypeptide): CD8A antibodies    
CD80 (CD80): CD80 antibodies CD80 ELISA Kits CD80 Proteins
CD86 (CD86 Molecule): CD86 antibodies CD86 ELISA Kits CD86 Proteins
CD8A - CD8: CD8A antibodies CD8A ELISA Kits CD8A Proteins
CD8B (CD8b Molecule): CD8B antibodies CD8B ELISA Kits CD8B Proteins
HLA-DRA - HLA Class II DR alpha: HLA-DRA antibodies HLA-DRA ELISA Kits HLA-DRA Proteins
HLA-DRB1 (HLA Class II DR beta 1): HLA-DRB1 antibodies HLA-DRB1 ELISA Kits HLA-DRB1 Proteins
HLA-DRB3 (HLA Class II DR beta 3): HLA-DRB3 antibodies   HLA-DRB3 Proteins
HLADRB4 - HLA Class II DR beta 4: HLADRB4 antibodies   HLADRB4 Proteins
HLA-ABC - HLA-ABC: HLA-ABC antibodies    
LAT (Linker For Activation of T Cells): LAT antibodies LAT ELISA Kits LAT Proteins
HLA-A (Major Histocompatibility Complex, Class I, A): HLA-A antibodies HLA-A ELISA Kits HLA-A Proteins
HLA-DPA1 - Major Histocompatibility Complex, Class II, DP alpha 1: HLA-DPA1 antibodies HLA-DPA1 ELISA Kits HLA-DPA1 Proteins
HLA-DPB1 (Major Histocompatibility Complex, Class II, DP beta 1): HLA-DPB1 antibodies   HLA-DPB1 Proteins
HLADQA1 - Major Histocompatibility Complex, Class II, DQ alpha 1: HLADQA1 antibodies HLADQA1 ELISA Kits HLADQA1 Proteins
HLA-DQA2 - Major Histocompatibility Complex, Class II, DQ alpha 2: HLA-DQA2 antibodies   HLA-DQA2 Proteins
HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ beta 1): HLA-DQB1 antibodies HLA-DQB1 ELISA Kits HLA-DQB1 Proteins
HLA-DQB2 (Major Histocompatibility Complex, Class II, DQ beta 2): HLA-DQB2 antibodies   HLA-DQB2 Proteins
HLA-DRB5 (Major Histocompatibility Complex, Class II, DR beta 5): HLA-DRB5 antibodies HLA-DRB5 ELISA Kits HLA-DRB5 Proteins
SHC1 (SHC (Src Homology 2 Domain Containing) Transforming Protein 1): SHC1 antibodies SHC1 ELISA Kits SHC1 Proteins
SLC25A20 - Solute Carrier Family 25 (Carnitine/acylcarnitine Translocase), Member 20: SLC25A20 antibodies SLC25A20 ELISA Kits SLC25A20 Proteins
TRAF6 (TNF Receptor-Associated Factor 6): TRAF6 antibodies TRAF6 ELISA Kits TRAF6 Proteins
TMEM189 (Transmembrane Protein 189): TMEM189 antibodies TMEM189 ELISA Kits TMEM189 Proteins

Adaptor Proteins and Regulators

Antigens in this category:
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
LCP2 (Lymphocyte Cytosolic Protein 2 (SH2 Domain Containing Leukocyte Protein of 76kDa)): LCP2 antibodies LCP2 ELISA Kits LCP2 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
PAG1 (phosphoprotein Associated with Glycosphingolipid Microdomains 1): PAG1 antibodies PAG1 ELISA Kits PAG1 Proteins
PTPN11 (Protein tyrosine Phosphatase, Non-Receptor Type 11): PTPN11 antibodies PTPN11 ELISA Kits PTPN11 Proteins
PTPRC - CD45: PTPRC antibodies PTPRC ELISA Kits PTPRC Proteins
PTPN6 (Protein-tyrosine Phosphatase 1C): PTPN6 antibodies PTPN6 ELISA Kits PTPN6 Proteins
SH3BP2 - SH3-Domain Binding Protein 2: SH3BP2 antibodies SH3BP2 ELISA Kits SH3BP2 Proteins

GEFs and PLCs (Ca2+ regulated)

Antigens in this category:
CBL (Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence): CBL antibodies CBL ELISA Kits CBL Proteins
CDC42 (Cell Division Cycle 42): CDC42 antibodies CDC42 ELISA Kits  
CDC42 (Cell Division Cycle 42 (GTP Binding Protein, 25kDa)): CDC42 antibodies CDC42 ELISA Kits CDC42 Proteins
FLNA - Filamin A: FLNA antibodies FLNA ELISA Kits FLNA Proteins
ORAI1 (ORAI Calcium Release-Activated Calcium Modulator 1): ORAI1 antibodies ORAI1 ELISA Kits  
PTEN (Phosphatase and Tensin Homolog): PTEN antibodies    
PIPLC - Phosphoinositide-Specific phospholipase C:   PIPLC ELISA Kits  
PLC (Phospholipase C): PLC antibodies PLC ELISA Kits PLC Proteins
PLC1 - Phospholipase C 1: PLC1 antibodies    
PLCG1 - Phospholipase C gamma 1: PLCG1 antibodies PLCG1 ELISA Kits PLCG1 Proteins
RAP1A (RAP1A, Member of RAS Oncogene Family): RAP1A antibodies RAP1A ELISA Kits RAP1A Proteins
RASSF5 (Ras Association (RalGDS/AF-6) Domain Family Member 5): RASSF5 antibodies RASSF5 ELISA Kits RASSF5 Proteins
RASGRP1 - RAS Guanyl Releasing Protein 1 (Calcium and DAG-Regulated): RASGRP1 antibodies RASGRP1 ELISA Kits RASGRP1 Proteins
RASGRP2 (RAS Guanyl Releasing Protein 2 (Calcium and DAG-Regulated)): RASGRP2 antibodies RASGRP2 ELISA Kits RASGRP2 Proteins
SOS1 (Son of Sevenless Homolog 1 (Drosophila)): SOS1 antibodies SOS1 ELISA Kits SOS1 Proteins
STIM1 (Stromal Interaction Molecule 1): STIM1 antibodies STIM1 ELISA Kits STIM1 Proteins
TRPV6 (Transient Receptor Potential Cation Channel, Subfamily V, Member 6): TRPV6 antibodies TRPV6 ELISA Kits TRPV6 Proteins
VASP (Vasodilator-Stimulated phosphoprotein): VASP antibodies VASP ELISA Kits VASP Proteins
VAV1 (Vav 1 Oncogene): VAV1 antibodies VAV1 ELISA Kits VAV1 Proteins

Kinases

ZAP70 (zeta-Chain (TCR) Associated Protein Kinase 70kDa):

Antigens in this category:
PDPK1 (3-phosphoinositide Dependent Protein Kinase-1): PDPK1 antibodies PDPK1 ELISA Kits PDPK1 Proteins
AURKB - Aurora Kinase B: AURKB antibodies AURKB ELISA Kits AURKB Proteins
CSK (C-Src tyrosine Kinase): CSK antibodies CSK ELISA Kits CSK Proteins
CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase): CHUK antibodies CHUK ELISA Kits CHUK Proteins
DRB1 - Dopamine Receptor Binding 1: DRB1 antibodies    
DBNL (Drebrin-Like): DBNL antibodies DBNL ELISA Kits DBNL 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
ITK (IL2-Inducible T-Cell Kinase): ITK antibodies ITK ELISA Kits ITK Proteins
INPP5D - Inositol Polyphosphate-5-Phosphatase, 145kDa: INPP5D antibodies INPP5D ELISA Kits INPP5D Proteins
LCK (Lymphocyte-Specific Protein tyrosine Kinase): LCK antibodies LCK ELISA Kits LCK 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
PAK1 (P21-Activated Kinase 1): PAK1 antibodies PAK1 ELISA Kits PAK1 Proteins
PAK2 (P21-Activated Kinase 2): PAK2 antibodies PAK2 ELISA Kits PAK2 Proteins
PIK3CA (Phosphoinositide-3-Kinase, Catalytic, alpha Polypeptide): PIK3CA antibodies PIK3CA ELISA Kits PIK3CA Proteins
PI3K - Phosphotylinosital 3 Kinase: PI3K antibodies PI3K ELISA Kits PI3K Proteins
PKC - Protein Kinase C: PKC antibodies PKC ELISA Kits  
PKCa - PKC alpha: PKCa antibodies PKCa ELISA Kits PKCa Proteins
PRKCB - PKC beta: PRKCB antibodies PRKCB ELISA Kits PRKCB Proteins
PRKCE (Protein Kinase C, epsilon): PRKCE antibodies PRKCE ELISA Kits PRKCE Proteins
PRKCQ - PKC theta: PRKCQ antibodies PRKCQ ELISA Kits PRKCQ Proteins
RIPK2 (Receptor-Interacting Serine-threonine Kinase 2): RIPK2 antibodies RIPK2 ELISA Kits RIPK2 Proteins
TAB2 (TGF-beta Activated Kinase 1/MAP3K7 Binding Protein 2): TAB2 antibodies TAB2 ELISA Kits TAB2 Proteins
AKT1 - AKT: AKT1 antibodies AKT1 ELISA Kits AKT1 Proteins

Transcription Factors

Antigens in this category:
BCL10 (B-Cell CLL/lymphoma 10): BCL10 antibodies BCL10 ELISA Kits BCL10 Proteins
CARD11 (Caspase Recruitment Domain Family, Member 11): CARD11 antibodies CARD11 ELISA Kits CARD11 Proteins
CCK - Cholecystokinin: CCK antibodies CCK ELISA Kits CCK Proteins
CREBBP - CBP: CREBBP antibodies CREBBP ELISA Kits CREBBP 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
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
NR2C2 - Nuclear Receptor Subfamily 2, Group C, Member 2: NR2C2 antibodies NR2C2 ELISA Kits NR2C2 Proteins
RIP2 (ROP Interactive Partner 2): RIP2 antibodies    
UBE2V1 (Ubiquitin-Conjugating Enzyme E2 Variant 1): UBE2V1 antibodies UBE2V1 ELISA Kits UBE2V1 Proteins
UBE2N (Ubiquitin-Conjugating Enzyme E2N): UBE2N antibodies UBE2N ELISA Kits UBE2N Proteins
RELA (V-Rel Reticuloendotheliosis Viral Oncogene Homolog A (Avian)):     RELA Proteins