Cluster of Differentiation (CD) Protein Overview

CD protein (Cluster of Differentiation proteins) is a kind of membrane protein expressed on the surface of immune cells, which is mainly used to mark and identify specific types and functional states of immune cells. CD proteins are identified by antibody labeling and immunophenotyping techniques, and hundreds of CD proteins have been identified so far. CD protein plays an important role in immune cell recognition, activation, proliferation and regulation. They mediate cell-cell interactions, signaling and localization of immune cells. Specific CD proteins are expressed on the surface of different types of immune cells, such as T cells, B cells, macrophages and natural killer cells.

By studying the expression and function of CD protein, we can better understand the types, differentiation status and functional characteristics of immune cells. This is of great significance for studying the normal function of the immune system, the pathogenesis of immune-related diseases, and developing new immunotherapy strategies.

As a kind of membrane protein expressed on the surface of immune cells, CD protein plays a key role in the recognition and regulation of immune cells.

Fig.1 Numbers and types of cluster of differentiation markers. [1]
Fig.1 Numbers and types of cluster of differentiation markers. [1]

Research field of CD Protein

The research field of CD protein is very extensive and involves many fields. The following are some of the main areas of research for CD proteins:

  1. Immune cell typing and identification: CD protein is widely used to label and identify different types of immune cells, such as T cells, B cells, macrophages, natural killer cells, etc. Researchers use the expression patterns and combinations of CD proteins to type and identify immune cells to gain insight into the types, differentiation status, and functional properties of immune cells.
  2. Immunomodulation and immunotherapy: CD protein plays an important role in immunomodulation and immunotherapy. Researchers study the regulatory mechanism of CD protein in the process of immune cell activation, proliferation, apoptosis, etc., as well as the interaction between CD protein and its ligands, and develop antibody drugs and immunotherapy against CD protein for the treatment of tumors, Diseases such as autoimmune diseases and transplant rejection.
  3. Immune-related diseases: CD protein is also of great significance in the research of immune-related diseases. Researchers study the relationship between the abnormal expression and dysfunction of CD protein and the occurrence and development of autoimmune diseases, infectious diseases and inflammatory responses. Find new targets and strategies for the treatment of immune-related diseases by in-depth study of the mechanism of action of CD protein.
  4. Neuroimmunology: In recent years, CD protein has received more and more attention in neuroimmunology research. Researchers study the expression and regulation of CD proteins in the nervous system, and their roles in neuroinflammation, neurodegenerative diseases, and neuroimmune regulation. This has important implications for understanding neuroimmune interactions and developing treatments for related diseases.

The research field of CD protein involves many aspects such as immune cell typing and identification, immune regulation and immunotherapy, immune-related diseases and neuroimmunology. Through the study of CD protein, we can better understand the characteristics and functions of immune cells, and promote the development of immunotherapy and disease treatment.

Popular CD Protein

CD3

CD3 is a complex composed of four subunits, CD3δ, CD3ε, CD3γ and CD3ζ, and is mainly expressed on the surface of T cells. Together with the T cell receptor (TCR), they form the TCR-CD3 complex, which is involved in the recognition and signal transduction of T cells.

The CD3 complex plays a key role in T cell activation and immune response. When the TCR binds to an antigen, the CD3 complex transmits a signal that leads to T cell activation and proliferation, which in turn initiates an immune response against the antigen. Different subunits in the CD3 complex have specific functions, among which the CD3ζ subunit is a key component of signaling.

CD3 is also widely used in immunology research and clinical application. In terms of research, scientists can use CD3 antibody to label and identify T cells, and study the typing, activation and function of T cells. In terms of clinical application, CD3 antibody can be used to treat malignant tumors and autoimmune diseases.

Fig.2 Schematic representation of the T-cell receptor-CD3 complex.[1]
Fig.2 Schematic representation of the T-cell receptor-CD3 complex.[1]

CD4

CD4 is a membrane protein widely expressed on the surface of helper T cells (CD4+ T cells). It is a key molecule in the immune system, involved in regulating and coordinating immune responses.

The main function of CD4 is to play a role in the process of antigen recognition by T cell receptor (TCR). When TCR binds to an antigen, the CD4 molecule helps T cells recognize the antigen and activate an immune response by binding to major histocompatibility complex class II (MHC-II) molecules. CD4 is also involved in regulating the differentiation and function of T cells, such as promoting the differentiation of helper T cells to specific subsets, enhancing cytokine production and regulating the activation of other immune cells.

CD4 is also widely used in research and clinical applications. In terms of research, scientists use CD4 antibodies to identify and isolate CD4+ T cells to study their function, activation and regulatory mechanisms. In terms of clinical application, the expression level of CD4 can be used as one of the indicators for evaluating immune function and monitoring disease progression.

CD8

CD8 is a membrane protein mainly expressed on the surface of cytotoxic T cells (CD8+ T cells). It plays a key role in the immune response and cellular immunity. The CD8 protein has two isoforms: CD8α and CD8β. These two subtypes form the CD8 molecular complex, which is involved in the process of cellular immunity by binding to the T cell receptor (TCR). CD8 protein plays an important role in cellular immunity. By combining with MHC-I molecules, it helps T cells recognize and kill infected cells, tumor cells and abnormal cells themselves.

CD8+ T cells are called cytotoxic T cells or CTLs (Cytotoxic T Lymphocytes), which have the ability to directly kill infected cells. CD8 triggers the death of target cells by releasing cytotoxins and apoptotic signaling molecules. This cytotoxic activity is critical for clearing pathogenic infections and controlling tumor growth.

CD8 can also be used as a marker for immune monitoring and diagnosis. By detecting the expression level of CD8, it is possible to evaluate the cellular immune function, monitor the disease state and evaluate the therapeutic effect. In research and clinical practice, the expression level of CD8 is often used as an important indicator to evaluate immune activity and disease progression.

Fig.3 Lytic and non-lytic effector mechanisms of CD8+ T-cells.[2]
Fig.3 Lytic and non-lytic effector mechanisms of CD8+ T-cells.[2]

References:

[1] Várady G, Cserepes J, Németh A, Szabó E, Sarkadi B. Cell surface membrane proteins as personalized biomarkers: where we stand and where we are headed. Biomark Med. 2013;7(5):803-819. doi:10.2217/bmm.13.90 https://pubmed.ncbi.nlm.nih.gov/24044572/

[2] Franco R, Martínez-Pinilla E, Lanciego JL, Navarro G. Basic Pharmacological and Structural Evidence for Class A G-Protein-Coupled Receptor Heteromerization. Front Pharmacol. 2016;7:76. Published 2016 Mar 31. doi:10.3389/fphar.2016.00076 https://pubmed.ncbi.nlm.nih.gov/27065866/

[3] Perdomo-Celis F, Taborda NA, Rugeles MT. CD8+ T-Cell Response to HIV Infection in the Era of Antiretroviral Therapy. Front Immunol. 2019;10:1896. Published 2019 Aug 9. doi:10.3389/fimmu.2019.01896 https://pubmed.ncbi.nlm.nih.gov/31447862/

Target Name
(CD1 - CD199)
Alternative Name(s)
CD1b-
CD1dR3G1
CD2SRBC, T11
CD3eT3E, TCRE
CD3dT3D, OKT3
CD4-
CD5LEU1, T1
CD5L-
CD6OX52, T12, TP120
CD7LEU 9, GP40, TP41, Tp40
CD8aMAL, Leu2, p32
CD8bCD8B1, LYT3, Leu2, Ly3
CD9MIC3, BA2, DRAP-27, MRP-1
CD10Neprilysin, CALLA, SFE, MME, NEP
CD13ANPEP, APN, PEPN, LAP1, gp150
CD14-
CD16bFc-gamma RIII-beta, FCGR3B, FCG3, FCGR3, IGFR3
CD16aFc-gamma RIII-alpha, FCGR3A, FCG3, FCGR3, IGFR3
CD16-
CD18Integrin beta-2, ITGB2, MFI7, LAD, LCAMB, LFA-1
CD19B-lymphocyte surface antigen B4, MGC12802, CVID3
CD20B-lymphocyte surface antigen B1, Bp35, Leukocyte surface antigen Leu-16, MS4A2
CD21Complement receptor type 2, CR2, C3DR, Complement C3d receptor, Epstein-Barr virus receptor
CD22SIGLEC2, BL-CAM, T-cell surface antigen Leu-14
CD23Low affinity immunoglobulin epsilon Fc receptor, Fc epsilon RII, FCER2, CLEC4J
CD24CD24A
CD25Interleukin-2 receptor subunit alpha, IL2RA, TAC antigen, TCGFR
CD26DPP4, ADABP, ADCP2, DPPIV, TP103
CD27TNF receptor superfamily member 7, TNFRSF 7, CD27L receptor, T14, MGC20393, S152, Tp55
CD28TP44
CD29Integrin beta-1, ITGB1, Fibronectin receptor subunit beta, FNRB, GPIIA, MDF2, MSK12, VLAB
CD30L-
CD30TNF receptor superfamily member 8, TNFRSF8, Ki-1 antigen, D1S166E
CD31Platelet endothelial cell adhesion molecule, PECAM1
CD32B-
CD32A-
CD33p67, Sialic acid-binding Ig-like lectin 3 (SIGLEC3)
CD34-
CD36Fatty acid translocase, Glycoprotein IIIb, GP3B, GP4, GPIV, PASIV, SCARB3
CD37Tetraspanin 26, TSPAN26, GP52-40
CD38ADP ribosyl cyclase 1, NAD(+) nucleosidase
CD39NTPDase 1, TPDase
CD39L1-
CD40Bp50, p50
CD40LG-
CD42bPlatelet glycoprotein Ib alpha chain, BSS, GP1B
CD42cPlatelet glycoprotein Ib beta chain, GP1BB
CD43Leukosialin, Galactoglycoprotein, Leukocyte sialoglycoprotein, SPN, GPL115, LSN
CD44Epican, HUTCH-I, LHR, PGP-1, ECMR-III, IN, INLU, MC56, MDU2, MIC4, MUTCH-1
CD45Leukocyte common antigen, L-CA, PTPRC
CD46Membrane cofactor protein, TLX, MCP, TRA2.10
CD47Integrin associated protein, MER6, OA3
CD48BLAST1, BCM1, MEM-102, SLAMF2
CD50ICAM3, CDw50, ICAM-R
CD52Campath-1
CD53MOX44
CD54ICAM1, BB2
CD55Complement decay accelerating factor, DAF, CR, TC
CD56NCAM1, MSK39
CD57Human natural killer 1, HNK1, LEU7
CD58LFA3
CD59Protectin, MAC-inhibitory protein, MSK21
CD59a-
CD62EE-selectin, SELE, ELAM1, LECAM2
CD62LL-selectin, SELL, LAM1, LECAM1, LYAM1, Leu-8
CD62PP-selectin, SELP, LECAM3, GRMP, PADGEM
CD63LAMP-3, Granulophysin, MLA1, ME491
CD64IgG Fc receptor I, FCGR1A, IGFR1
CD66bCEACAM8, CD67, CGM6, NCA-95
CD67See CD66b
CD68SCARD1, KP1
CD69Activation inducer molecule, AIM, CLEC2C, EA1
CD70CD27L, TNFSF7
CD72LYB2
CD735\'-nucleotidase, NT5E, E5NT
CD74DHLAG, Ia-GAMMA, HLADG
CD79bB29, IGB
CD79aMB1, IGA
CD80B7-1
CD81TAPA1, Tetraspanin-28, S5.7
CD82KAI1, Tetraspanin-27, 4F9, C33, GR15, SAR2, ST6
CD83HB15, BL11
CD84LY9B, SLAMF5
CD85fLILRB7, ILT11, LIR9, LILRA5
CD85kLILRB4, ILT3, LIR5, HM18
CD85jLILRB1, ILT2, LIR1, MIR7
CD85iLILRA1, LIR6
CD85aLILRB3, ILT5, LIR3, HL9
CD85hLILRA2, ILT1, LIR7
CD85gLILRA4, ILT7
CD85bLILRA6, ILT8
CD85cLILRB5, LIR8
CD85eLILRA3, ILT6, LIR4
CD85dLILRB2, ILT4, LIR2, MIR10
CD86CD28LG2, B7-2, LAB72
CD87UPAR, PLAUR
CD89FCAR
CD90THY1
CD93C1qR, C1QR1, MXRA4
CD94KLRD1, NKG2
CD95Apoptosis antigen ligand, FASLG, APTL, TNFSF6, APO-1
CD96Tactile
CD97TM7LN1
CD984F2hc, SLC3A2, MDU1, NACAE
CD99L2-
CD99MIC2
CD100Semaphorin 4D, SEMA4D, M-sema G
CD102ICAM2
CD105Endoglin, ENG, END, ORW
CD106VCAM1, L1CAM
CD107aLAMP1
CD107bLAMP2
CD109FLJ38569
CD111Nectin1, PVRL1, HVEC
CD112Nectin2, PVRL2, HVEB
CD113Nectin3, PVRL3
CD114GCSFR, CSF3R
CD115CSF1R, FMS
CD116GM-CSF-R-alpha, GMCSFR, CSF2RA
CD117c-kit, KIT, SCFR
CD118LIFR, SWS, STWS
CD119IFNGR1
CD120aTNF Receptor I, TNFRSF1A, FPF
CD120bTNF Receptor II, TNFRSF1B
CD121aIL-1R type I, IL1R1
CD121bIL-1R type II, IL1R2
CD122IL2RB, P70-75
CD123IL3RA
CD124IL4RA, IL4R
CD125IL5RA, IL5R
CD126IL6R, gp80
CD127IL7R
CD129IL9R
CD130IL6ST, gp130
CD131IL3RB, IL5RB, CSF2RB
CD132IL2RG, IMD4, SCIDX
CD133Prominin-1, PROM1, AC133
CD134TNFRSF4, ACT35, OX40
CD135FLT3, FLK2, STK1
CD136RON, PTK8, MST1R
CD137TNFRSF9, ILA, 4-1BB
CD138Syndecan, SDC1, SYND1
CD140bPDGFR-beta, PDGFRB, JTK12
CD140aPDGFR-alpha, PDGFRA
CD141Thrombomodulin, THBD, THRM, BDCA-3
CD142Tissue factor, F3
CD144VE-cadherin, Cadherin-5, CDH5, 7B4
CD146MCAM, MUC18
CD147Basigin, BSG, 5F7, EMMPRIN, M6, OK, TCSF
CD148DEP1, PTPRJ, SCC1
CD150SLAM, SLAMF1, IPO-3
CD152CTLA-4
CD153CD30 ligand, TNFSF8
CD154CD40 ligand, Gp39, TRAP, HIGM1
CD155Poliovirus Receptor, NECL-5, TAGE4
CD156aADAM8, MS2
CD157BST-1
CD158dKIR2DL4, KIR-103AS
CD158fKIR2DL5, KIR2DL5.1, KIR2DL5.3
CD158b2NKAT-2, KIR2DL3, CL-6, p58
CD158aNKAT-1, KIR2DL1, CL-43, p58.1
CD159cNKG2C, KLRC2
CD159aNKG2A, KLRC1
CD160BY55, NK28
CD161NKR-P1A, KLRB1
CD162PSGL-1, SELPLG
CD163M130
CD164MUC-24, MGC-24, endoyn
CD166ALCAM, MEMD
CD167bDDR2, TKT, NTRKR3, TYRO10
CD167aDDR1, CAK, EDDR1, NTRK4, PTK3
CD170SIGLEC5, OB-BP2
CD171NCAM-L1, L1CAM, CAML1, SPG1
CD172aSHPS-1, SIRPA, PTPNS1
CD172gSIRPG, SIRPB2
CD177NB1 glycoprotein, HNA-2a
CD178Fas ligand, CD95 ligand, TNFSF6
CD180RP105, LY64
Target Name
(CD200 - )
Alternative Name(s)
CD200OX-2, MOX1
CD200R1-
CD200R1L-
CD200R4-
CD200R-
CD202bTIE2, TEK, TIE2, VMCM
CD204MSR1, SCARA1, phSR2
CD205DEC205, LY75, CLEC13B
CD206MMR, MRC1, CLEC13D
CD207Langerin, CLEC4K
CD208LAMP3, DCLAMP, TSC403
CD209DC-SIGN
CD210aIL10RA, IL10R1
CD212IL12RB1, MGC34454
CD213a1IL13RA1, NR4
CD213a2IL13RA2, IL13BP
CD215IL15RA
CD217IL17R, IL-17RA
CD218aIL18R1, IL1RRP, IL-1Rrp
CD218bIL18Rbeta, IL18RAP, ACPL
CD220Insulin receptor, INSR
CD221Insulin-like growth factor 1 receptor, IGF1R, JTK13
CD223LAG-3
CD225IFITM1, Leu-13, Sep-27
CD226DNAM-1, PTA1
CD227MUC1, PUM, EMA
CD228Melanotransferrin, MFI2, MAP97
CD229Ly9, SLAMF3
CD230PrP, PRNP, ASCR
CD231Tspan-7, TALLA-1, A15, TM4SF2b
CD235aGlycophorin-A, GYPA, MNS
CD236Glycophorin, GPC
CD239Lutheran blood group antigen, B-CAM
CD242ICAM-4, LW
CD2442B4, NAIL, SLAMF4
CD247TCR Z chain, CD3H
CD249EAP, Aminopeptidase A, ENPEP
CD252OX40L, TNFSF4, GP34
CD253Apo-2L, TRAIL, TNFSF10
CD254ODF, OPGK, RANKL, TRANCE, TNFSF11
CD257BAFF, TALL-1, TNFSF13B, BLYS, ZTNF4
CD258TNFRSF14, HVEM-L, LIGHT
CD261DR4, TRAIL-R1, TNFRSF10A, Apor2
CD262DR5, TRAIL-R2, TNFRSF10B, TRICKB
CD263DcR1, TRAIL-R3, TNFRSF10C, LIT, TRID
CD264DCR2, TRAIL-R4, TNFRSF10D, TRUNDD
CD265RANK, ODFR, TNFRSF11A, TRANCER
CD266TWEAKR, TNFRSF12A, FN14
CD267TACI, TNFRSF13B, CVID, TNFRSF14B
CD268BAFF receptor, TNFRSF13C
CD269BCMA
CD273PD-L2, B7-DC, PDCD1LG2
CD274PD-L1, B7-H1
CD275B7-H2, B7RP-1, ICOSLG, LICOS
CD276B7-H3
CD277BTN3A1, BTF5
CD278ICOS, AILIM
CD279PD-1, PDCD1, SLEB2
CD282TLR2, TIL4
CD283TLR3
CD284TLR4, TOLL, hToll
CD292BMPR-1A, ALK-3, ACVRLK3
CDw293BMPR-1B, ALK6
CD295LEP-R, OB-R
CD297ART4, DOK1
CD299CLEC4M, L-SIGN, DC-SIGNR
CD300LB-
CD300LG-
CD300aCMRF-35-H9, IRC1, IRp60, CLM8, MAIR
CD300cCMRF-35A, LIR
CD300eCLM-2, IREM-2
CD300fCLM-1, IREM-1, LMIR3
CD301CLEC10A, HML2
CD302DCL-1, BIMLEC
CD303CLEC4C, BCDA-2
CD306LAIR2
CD307bFcRL2, FCRH2, IRTA4
CD314NKG2D, KLRK1
CD316IGSF8, EWI-2, KCT-4, PGRL
CD317BST2, Tetherin
CD318CDCP1, SIMA135, gp140, Trask
CD319SLAMF7, CRACC, CS-1
CD320FDC-SM-8D6, TCbIR
CD321JAM-A, JAM-1, PAM-1, F11R, KAT
CD322JAM-B, JAM-2, VE-JAM
CD324E-Cadherin, CDH1
CD331FGFR1, BFGFR, FLT-2
CD332FGFR2, KGFR
CD333FGFR3, ACH, JTK4
CD334FGFR4, TKF, JTK2
CD335NCR1, NK-p46, LY94
CD336NCR2, NK-p44, LY95
CD337NCR3, NK-p30, LY117
CD339Jagged1, JAG1, AHD, AWS
CD340ERBB2, MLN 19, NEU, HER2
CD344Frizzled-4 (Fz-4), FzE4, EVR1
CD350Frizzled-10, Fz-10, FZD10
CD351FCAMR, FKSG87
CD352NTB-A, SLAMF6, KALI, Ly108
CD354TREM-1
CD355CRTAM
CD357TNFRSF18, AITR, GITR
CD358TNFRSF21, Death receptor 6 (DR6)
CD365HAVCR1, TIM-1
CD366HAVCR2, TIM-3, TIMD3
CD367CLEC4, DCIR, DDB27, CLECSF6
CD371CLEC12A, CLL-1, MICL, DCAL-2