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Cell Activation and Signaling in Lymphocytes

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Tissue-Specific Cell Signaling

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Abstract

Lymphocyte activation and proliferation are a result of a functional encounter between a lymphocyte bearing a clonotypic receptor that recognizes unique nonself-antigens and a cell that presents those specific antigens at its surface. Positive recognition of antigen by the T cell receptor of T lymphocytes, or by the B cell receptor of B lymphocytes, is then signaled to inner components of the cell through biochemical activation pathways. A number of adhesion molecules and co-receptors help to strengthen the interaction between the lymphocyte and the antigen presenting cell, and some of these surface proteins transduce signals that complement or amplify those delivered by the antigen receptor in a concerted action that modifies cellular behavior. B and T cell receptor-proximal signaling involves the extensive phosphorylation of intracellular effectors and adaptors that help to assemble large multi-protein complexes that transmit and diversify the received stimuli into the activation of an array of transcription factors that modify the transcriptional landscape of the cell and change cell behavior. The majority of the signaling steps are common to those of many different mammalian cell types. However, the extreme complexity of the lymphocyte signaling networks with many additional checkpoints and controlling steps endows lymphocytes with a remarkable capacity of regulating the outcome of activation that goes beyond the simple response to increased amounts of agonist. On the outcome of controlled lymphocyte activation depends the building of an effective immune response towards foreign or external aggression while avoiding self-reactivity against own components and development of autoimmunity.

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Abbreviations

AP1:

Activator protein 1

APC:

Antigen presenting Cell

BCL6:

B-cell lymphoma 6 protein

BCL10:

B-cell lymphoma/leukemia 10

BCR:

B Cell receptor

BLNK:

B-cell linker protein

BTLA:

B- and T-lymphocyte attenuator

CARD11:

Caspase recruitment domain-containing protein 11

CBL:

Casitas B-lineage lymphoma proto-oncogene

CD40LG:

CD40 ligand

CSK:

C-terminal Src kinase

cSMAC:

Central supramolecular activation cluster

CTLA4:

Cytotoxic T-lymphocyte protein 4

DAG:

1,2-Diacylglycerol

dSMAC:

Distal supramolecular activation cluster

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulated protein kinase

FYB1:

FYN-binding protein 1

FYN:

FGR/YES novel protein

GRAP2:

GRB2-related adapter protein 2

GRB2:

Growth factor receptor-bound protein 2

ICAM1:

Intercellular adhesion molecule 1

IgSF:

Immunoglobulin superfamily

IKKA:

Inhibitor of nuclear factor κB kinase A

IKZF1:

Ikaros family zinc finger protein 1

IL2:

Interleukin 2

INPP5D:

Inositol polyphosphate-5-phosphatase D

InsP3:

Inositol 1,4,5-trisphosphate

IRF8:

Interferon regulatory factor 8

ITAM:

Immunoreceptor tyrosine-based activation motif

ITGAL:

Integrin alpha-L

ITIM:

Immunoreceptor tyrosine-based inhibitory motif

ITK:

IL2-inducible T-cell tyrosine kinase

LAG3:

Lymphocyte-activation gene 3

LAT:

Linker for activation of T cells

LCK:

Lymphocyte-specific protein-tyrosine kinase

LCP2:

Lymphocyte cytosolic protein 2

LYN:

Lck/Yes-related novel protein tyrosine kinase

MALT1:

Mucosa-associated lymphoid tissue lymphoma translocation protein 1

MAP2K1:

Mitogen-activated protein kinase kinase 1

mIg:

Membrane immunoglobulin

NCK1:

Non-catalytic region of tyrosine kinase adaptor protein 1

NFAT:

Nuclear factor of activated T-cells

NFKB:

Nuclear factor κB

NFKBI:

NFKB inhibitor IκB

NTAL:

Non-T cell activation linker

ORAI1:

Calcium release-activated calcium channel protein 1

PAG1:

Phosphoprotein associated with glycosphingolipid-enriched microdomains 1

PD1:

Programmed cell death protein 1

PDPK1:

3-Phosphoinositide-dependent protein kinase 1

PH:

Pleckstrin homology

PIK3:

Phosphatidylinositol 3-kinase

PIK3C:

Catalytic subunit of phosphatidylinositol 3-kinase

PIK3R:

Regulatory subunit of phosphatidylinositol 3-kinase

PKC:

Protein kinase C

PLCG:

Phospholipase C-γ

PLCG1:

Phospholipase C-γ1

PLCG2:

Phospholipase C-γ2

pMHC:

Peptide-MHC complex

POU2F1:

POU domain, class 2, transcription factor 1

PRDM1:

PR domain zinc finger protein 1

PRKCB:

PKC isoform β

PRKCQ:

PKC isoform θ

pSMAC:

Peripheral supramolecular activation cluster

PtdIns(4,5)P2:

Phosphatidylinositol 4,5-bisphosphate

PtdIns(3,4,5)P3:

Phosphatidylinositol 3,4,5-trisphosphate  

PTK:

Protein tyrosine kinase

PTPN6:

Protein tyrosine phosphatase non-receptor type 6

PTPN11:

Protein  tyrosine phosphatase non-receptor type II

RASA1:

RAS GTPase-activating protein 1

RASGRP1:

RAS guanyl-releasing protein 1

RASGRP3:

RAS guanyl-releasing protein 3

RTK:

Receptor tyrosine kinases

SH:

SRC homology

SIGLEC:

Sialic acid binding Ig-like lectin

SOS1:

Son of sevenless homolog 1

SRCR:

Scavenger receptor cysteine-rich

SYK:

Spleen tyrosine kinase

TCR:

 T cell receptor

TGF:

Transforming growth factor

TIGIT:

T cell immunoreceptor with Ig and ITIM domains

TNFR:

Tumor necrosis factor receptor

TRAF6:

TNF receptor-associated factor 6

XBP1:

X-box-binding protein 1

ZAP-70:

Z-associated protein-70

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Acknowledgments

This work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-032296 (PTDC/MED-IMU/32296/2017). SNH is recipient of a studentship SFRH/BD/133312/2017 from FCT.

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  1. IBMC—Instituto de Biologia Molecular e Celular, Porto, Portugal

    Alexandre M. Carmo & Sónia N. Henriques

  2. i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

    Alexandre M. Carmo & Sónia N. Henriques

  3. Programa Doutoral em Biologia Molecular e Celular (MCbiology), Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

    Sónia N. Henriques

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  1. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal

    Joana Vieira Silva

  2. Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium

    Maria João Freitas

  3. Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine—iBiMED, University of Aveiro, Aveiro, Portugal

    Margarida Fardilha

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Carmo, A.M., Henriques, S.N. (2020). Cell Activation and Signaling in Lymphocytes. In: Silva, J.V., Freitas, M.J., Fardilha, M. (eds) Tissue-Specific Cell Signaling. Springer, Cham. https://doi.org/10.1007/978-3-030-44436-5_5

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