CD4

Last updated
CD4
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CD4 , CD4mut, CD4 molecule, OKT4D, IMD79
External IDs OMIM: 186940; MGI: 88335; HomoloGene: 513; GeneCards: CD4; OMA:CD4 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

920

12504

Ensembl

ENSG00000010610

ENSMUSG00000023274

UniProt

P01730

P06332

RefSeq (mRNA)

NM_013488

RefSeq (protein)

NP_038516

Location (UCSC) Chr 12: 6.79 – 6.82 Mb Chr 6: 124.84 – 124.87 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
CD4, Cluster of differentiation 4, extracellular
PDB 1wip EBI.jpg
structure of T cell surface glycoprotein cd4, monoclinic crystal form
Identifiers
SymbolCD4-extrcel
Pfam PF09191
InterPro IPR015274
SCOP2 1cid / SCOPe / SUPFAM
OPM superfamily 193
OPM protein 2klu
CDD cd07695
Membranome 27
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Image of CD4 co-receptor binding to MHC (Major Histocompatibility Complex) non-polymorphic region. CD4 correceptor.png
Image of CD4 co-receptor binding to MHC (Major Histocompatibility Complex) non-polymorphic region.

In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). CD4 is found on the surface of immune cells such as helper T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984. [5] In humans, the CD4 protein is encoded by the CD4 gene. [6] [7]

CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T helper cells or T4 cells. They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 killer cells, which then destroy the infectious particle. If CD4 cells become depleted, for example in untreated HIV infection, or following immune suppression prior to a transplant, the body is left vulnerable to a wide range of infections that it would otherwise have been able to fight.

Structure

Schematic representation of CD4 receptor. CD4 receptor.png
Schematic representation of CD4 receptor.

Like many cell surface receptors/markers, CD4 is a member of the immunoglobulin superfamily.

It has four immunoglobulin domains (D1 to D4) that are exposed on the extracellular surface of the cell:

The immunoglobulin variable (IgV) domain of D1 adopts an immunoglobulin-like β-sandwich fold with seven β-strands in two β-sheets, in a Greek key topology. [8]

CD4 interacts with the β2-domain of MHC class II molecules through its D1 domain. T cells displaying CD4 molecules (and not CD8) on their surface, therefore, are specific for antigens presented by MHC II and not by MHC class I (they are MHC class II-restricted). MHC class I contains Beta-2 microglobulin.[ citation needed ]

The short cytoplasmic/intracellular tail (C) of CD4 contains a special sequence of amino acids that allow it to recruit and interact with the tyrosine kinase Lck.[ citation needed ]

Function

CD4 is a co-receptor of the T cell receptor (TCR) and assists the latter in communicating with antigen-presenting cells. The TCR complex and CD4 bind to distinct regions of the antigen-presenting MHC class II molecule. The extracellular D1 domain of CD4 binds to the β2 region of MHC class II. The resulting close proximity between the TCR complex and CD4 allows the tyrosine kinase Lck bound to the cytoplasmic tail of CD4 [9] to phosphorylate tyrosine residues of immunoreceptor tyrosine activation motifs (ITAMs) on the cytoplasmic domains of CD3 [10] to amplify the signal generated by the TCR. Phosphorylated ITAMs on CD3 recruit and activate SH2 domain-containing protein tyrosine kinases (PTK), such as ZAP70, to further mediate downstream signalling through tyrosine phosphorylation. These signals lead to the activation of transcription factors, including NF-κB, NFAT, AP-1, to promote T cell activation. [11]

Conservation of their respective cytoplasmic tail motifs, CxC/H in the case of CD4 and an ITIM-like motif in the case of LAG-3, supports that competition between CD4 and LAG-3 for binding of kinase LCK is a conserved core part of the jawed vertebrate immune system. CD4 and LAG-3 with opposing functions.png
Conservation of their respective cytoplasmic tail motifs, CxC/H in the case of CD4 and an ITIM-like motif in the case of LAG-3, supports that competition between CD4 and LAG-3 for binding of kinase LCK is a conserved core part of the jawed vertebrate immune system.

CD4 is closely related to LAG-3, [12] and together they form an evolutionary conserved system from the level of sharks competing for binding Lck by conserved motifs in their cytoplasmic tails: [13] CD4 through a Cys-X-Cys/His motif [14] and LAG-3 through an immunoreceptor tyrosine-based inhibition motif like (ITIM-like) motif. [13] [15] [16] LAG-3, which is an inhibitory receptor, is upregulated in activated T cells as a kind of negative feedback loop.

Other interactions

CD4 has also been shown to interact with SPG21, [17] and Uncoordinated-119 (Unc-119). [18]

Disease

HIV infection

HIV-1 uses CD4 to gain entry into host T-cells and achieves this through its viral envelope protein known as gp120. [19] The binding to CD4 creates a shift in the conformation of gp120 allowing HIV-1 to bind to a co-receptor expressed on the host cell. These co-receptors are chemokine receptors CCR5 or CXCR4. Following a structural change in another viral protein (gp41), HIV inserts a fusion peptide into the host cell that allows the outer membrane of the virus to fuse with the cell membrane.

HIV pathology

HIV infection leads to a progressive reduction in the number of T cells expressing CD4. Medical professionals refer to the CD4 count to decide when to begin treatment during HIV infection, although recent medical guidelines have changed to recommend treatment at all CD4 counts as soon as HIV is diagnosed. A CD4 count measures the number of T cells expressing CD4. While CD4 counts are not a direct HIV test—e.g. they do not check the presence of viral DNA, or specific antibodies against HIV—they are used to assess the immune system of a patient.[ citation needed ]

National Institutes of Health guidelines recommend treatment of any HIV-positive individuals, regardless of CD4 count [20] Normal blood values are usually expressed as the number of cells per microliter (μL, or equivalently, cubic millimeter, mm3) of blood, with normal values for CD4 cells being 500–1200 cells/mm3. [21] Patients often undergo treatments when the CD4 counts reach a level of 350 cells per microliter in Europe but usually around 500/μL in the US; people with less than 200 cells per microliter are at high risk of contracting AIDS defined illnesses. Medical professionals also refer to CD4 tests to determine efficacy of treatment.[ citation needed ]

Viral load testing provides more information about the efficacy for therapy than CD4 counts. [22] For the first 2 years of HIV therapy, CD4 counts may be done every 3–6 months. [22] If a patient's viral load becomes undetectable after 2 years then CD4 counts might not be needed if they are consistently above 500/mm3. [22] If the count remains at 300–500/mm3, then the tests can be done annually. [22] It is not necessary to schedule CD4 counts with viral load tests and the two should be done independently when each is indicated. [22]

Reference ranges for blood tests of white blood cells, comparing CD4+ cell amount (shown in green-yellow) with other cells. Reference ranges for blood tests - white blood cells.png
Reference ranges for blood tests of white blood cells, comparing CD4+ cell amount (shown in green-yellow) with other cells.

Other diseases

CD4 continues to be expressed in most neoplasms derived from T helper cells. It is therefore possible to use CD4 immunohistochemistry on tissue biopsy samples to identify most forms of peripheral T cell lymphoma and related malignant conditions. [23] The antigen has also been associated with a number of autoimmune diseases such as vitiligo and type I diabetes mellitus. [24]

T-cells play a large part in autoinflammatory diseases. [25] When testing a drug's efficacy or studying diseases, it is helpful to quantify the amount of T-cells on fresh-frozen tissue with CD4+, CD8+, and CD3+ T-cell markers (which stain different markers on a T-cell – giving different results). [26]

See also

Related Research Articles

<span class="mw-page-title-main">T cell</span> White blood cells of the immune system

T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface.

<span class="mw-page-title-main">Cytotoxic T cell</span> T cell that kills infected, damaged or cancerous cells

A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pathogens (such as viruses or bacteria), or cells that are damaged in other ways.

<span class="mw-page-title-main">T helper cell</span> Type of immune cell

The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considered essential in B cell antibody class switching, breaking cross-tolerance in dendritic cells, in the activation and growth of cytotoxic T cells, and in maximizing bactericidal activity of phagocytes such as macrophages and neutrophils. CD4+ cells are mature Th cells that express the surface protein CD4. Genetic variation in regulatory elements expressed by CD4+ cells determines susceptibility to a broad class of autoimmune diseases.

<span class="mw-page-title-main">T-cell receptor</span> Protein complex on the surface of T cells that recognizes antigens

The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR.

CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR). Along with the TCR, the CD8 co-receptor plays a role in T cell signaling and aiding with cytotoxic T cell-antigen interactions.

<span class="mw-page-title-main">Fc receptor</span> Surface protein important to the immune system

In immunology, an Fc receptor is a protein found on the surface of certain cells – including, among others, B lymphocytes, follicular dendritic cells, natural killer cells, macrophages, neutrophils, eosinophils, basophils, human platelets, and mast cells – that contribute to the protective functions of the immune system. Its name is derived from its binding specificity for a part of an antibody known as the Fc region. Fc receptors bind to antibodies that are attached to infected cells or invading pathogens. Their activity stimulates phagocytic or cytotoxic cells to destroy microbes, or infected cells by antibody-mediated phagocytosis or antibody-dependent cell-mediated cytotoxicity. Some viruses such as flaviviruses use Fc receptors to help them infect cells, by a mechanism known as antibody-dependent enhancement of infection.

A co-receptor is a cell surface receptor that binds a signalling molecule in addition to a primary receptor in order to facilitate ligand recognition and initiate biological processes, such as entry of a pathogen into a host cell.

<span class="mw-page-title-main">Tyrosin-protein kinase Lck</span> Lymphocyte protein

Tyrosin-protein kinase Lck is a 56 kDa protein that is found inside lymphocytes and encoded in the human by the LCK gene. The Lck is a member of Src kinase family (SFK) and is important for the activation of T-cell receptor (TCR) signaling in both naive T cells and effector T cells. The role of Lck is less prominent in the activation or in the maintenance of memory CD8 T cells in comparison to CD4 T cells. In addition, the constitutive activity of the mouse Lck homolog varies among memory T cell subsets. It seems that in mice, in the effector memory T cell (TEM) population, more than 50% of Lck is present in a constitutively active conformation, whereas less than 20% of Lck is present as active form in central memory T cells. These differences are due to differential regulation by SH2 domain–containing phosphatase-1 (Shp-1) and C-terminal Src kinase.

<span class="mw-page-title-main">CD28</span> Mammalian protein found in humans

CD28 is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor (TCR) can provide a potent signal for the production of various interleukins.

<span class="mw-page-title-main">Immunological synapse</span> Interface between lymphocyte and target cell

In immunology, an immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as a T cell, B cell, or natural killer cell. The interface was originally named after the neuronal synapse, with which it shares the main structural pattern. An immunological synapse consists of molecules involved in T cell activation, which compose typical patterns—activation clusters. Immunological synapses are the subject of much ongoing research.

<span class="mw-page-title-main">HLA-DRA</span> Protein-coding gene in the species Homo sapiens

HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms.

MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a T cell can interact with a self-major histocompatibility complex molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule.

In immunology, a naive T cell (Th0 cell) is a T cell that has differentiated in the thymus, and successfully undergone the positive and negative processes of central selection in the thymus. Among these are the naive forms of helper T cells (CD4+) and cytotoxic T cells (CD8+). Any naive T cell is considered immature and, unlike activated or memory T cells, has not encountered its cognate antigen within the periphery. After this encounter, the naive T cell is considered a mature T cell.

<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.

<span class="mw-page-title-main">CD3G</span> Protein-coding gene in the species Homo sapiens

T-cell surface glycoprotein CD3 gamma chain is a protein that in humans is encoded by the CD3G gene.

<span class="mw-page-title-main">Lymphocyte-activation gene 3</span>

Lymphocyte-activation gene 3, also known as LAG-3, is a protein which in humans is encoded by the LAG3 gene. LAG3, which was discovered in 1990 and was designated CD223 after the Seventh Human Leucocyte Differentiation Antigen Workshop in 2000, is a cell surface molecule with diverse biological effects on T cell function but overall has an immune inhibitory effect. It is an immune checkpoint receptor and as such is the target of various drug development programs by pharmaceutical companies seeking to develop new treatments for cancer and autoimmune disorders. In soluble form it is also being developed as a cancer drug in its own right.

<span class="mw-page-title-main">CD8A</span> Protein-coding gene in the species Homo sapiens

CD8a, is a human gene.

Immunoevasins are proteins expressed by some viruses that enable the virus to evade immune recognition by interfering with MHC I complexes in the infected cell, therefore blocking the recognition of viral protein fragments by CD8+ cytotoxic T lymphocytes. Less frequently, MHC II antigen presentation and induced-self molecules may also be targeted. Some viral immunoevasins block peptide entry into the endoplasmic reticulum (ER) by targeting the TAP transporters. Immunoevasins are particularly abundant in viruses that are capable of establishing long-term infections of the host, such as herpesviruses.

Kinetic-segregation is a model proposed for the mechanism of T-cell receptor (TCR) triggering. It offers an explanation for how TCR binding to its ligand triggers T-cell activation, based on size-sensitivity for the molecules involved. Simon J. Davis and Anton van der Merwe, University of Oxford, proposed this model in 1996. According to the model, TCR signalling is initiated by segregation of phosphatases with large extracellular domains from the TCR complex when binding to its ligand, allowing small kinases to phosphorylate intracellular domains of the TCR without inhibition. Its might also be applicable to other receptors of the Non-catalytic tyrosine-phosphorylated receptors family such as CD28.

<span class="mw-page-title-main">Killer cell immunoglobulin-like receptor 2DL3</span>

KIR2DL3, Killer cell immunoglobulin-like receptor 2DL3 is a transmembrane glycoprotein expressed by the natural killer cells and the subsets of the T cells. The KIR genes are polymorphic, which means that they have many different alleles. The KIR genes are also extremely homologous, which means that they are similar in position, structure and evolutionary origin, but not necessarily in function.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000010610 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023274 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Bernard A, Boumsell L, Hill C (1984). "Joint Report of the First International Workshop on Human Leucocyte Differentiation Antigens by the Investigators of the Participating Laboratories". In Bernard A, Boumsell L, Dausset J, Milstein C, Schlossman SF (eds.). Leucocyte typing: human leucocyte differentiation antigens detected by monoclonal antibodies: specification, classification, nomenclature. Berlin: Springer. pp. 45–48. doi:10.1007/978-3-642-68857-7_3. ISBN   0-387-12056-4. Report on the first international references workshop sponsored by INSERM, WHO and IUIS
  6. ↑ Isobe M, Huebner K, Maddon PJ, Littman DR, Axel R, Croce CM (June 1986). "The gene encoding the T-cell surface protein T4 is located on human chromosome 12". Proceedings of the National Academy of Sciences of the United States of America. 83 (12): 4399–4402. Bibcode:1986PNAS...83.4399I. doi: 10.1073/pnas.83.12.4399 . PMC   323740 . PMID   3086883.
  7. ↑ Ansari-Lari MA, Muzny DM, Lu J, Lu F, Lilley CE, Spanos S, et al. (April 1996). "A gene-rich cluster between the CD4 and triosephosphate isomerase genes at human chromosome 12p13". Genome Research. 6 (4): 314–326. doi: 10.1101/gr.6.4.314 . PMID   8723724.
  8. ↑ Brady RL, Dodson EJ, Dodson GG, Lange G, Davis SJ, Williams AF, Barclay AN (May 1993). "Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains". Science. 260 (5110): 979–983. Bibcode:1993Sci...260..979B. doi:10.1126/science.8493535. PMID   8493535.
  9. ↑ Rudd CE, Trevillyan JM, Dasgupta JD, Wong LL, Schlossman SF (July 1988). "The CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (pp58) from human T lymphocytes". Proceedings of the National Academy of Sciences of the United States of America. 85 (14): 5190–5194. Bibcode:1988PNAS...85.5190R. doi: 10.1073/pnas.85.14.5190 . PMC   281714 . PMID   2455897.
  10. ↑ Barber EK, Dasgupta JD, Schlossman SF, Trevillyan JM, Rudd CE (May 1989). "The CD4 and CD8 antigens are coupled to a protein-tyrosine kinase (p56lck) that phosphorylates the CD3 complex". Proceedings of the National Academy of Sciences of the United States of America. 86 (9): 3277–3281. Bibcode:1989PNAS...86.3277B. doi: 10.1073/pnas.86.9.3277 . PMC   287114 . PMID   2470098.
  11. ↑ Owens JA, Punt J, Stranford SA, Jones PP (2013). Kuby Immunology (7th ed.). New York: W.H. Freeman. pp. 100–101. ISBN   978-14641-3784-6.
  12. ↑ Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, Viegas-Pequignot E, Hercend T (May 1990). "LAG-3, a novel lymphocyte activation gene closely related to CD4". The Journal of Experimental Medicine. 171 (5): 1393–1405. doi:10.1084/jem.171.5.1393. PMC   2187904 . PMID   1692078.
  13. 1 2 Takizawa F, Hashimoto K, Miyazawa R, Ohta Y, Veríssimo A, Flajnik MF, et al. (2023-12-21). "CD4 and LAG-3 from sharks to humans: related molecules with motifs for opposing functions". Frontiers in Immunology. 14: 1267743. doi: 10.3389/fimmu.2023.1267743 . PMC   10768021 . PMID   38187381.
  14. ↑ Kim PW, Sun ZY, Blacklow SC, Wagner G, Eck MJ (September 2003). "A zinc clasp structure tethers Lck to T cell coreceptors CD4 and CD8". Science. 301 (5640): 1725–1728. Bibcode:2003Sci...301.1725K. doi:10.1126/science.1085643. PMID   14500983. S2CID   32336829.
  15. ↑ Ohashi K, Takizawa F, Tokumaru N, Nakayasu C, Toda H, Fischer U, et al. (August 2010). "A molecule in teleost fish, related with human MHC-encoded G6F, has a cytoplasmic tail with ITAM and marks the surface of thrombocytes and in some fishes also of erythrocytes". Immunogenetics. 62 (8): 543–559. doi:10.1007/s00251-010-0460-1. PMID   20614118. S2CID   12282281.
  16. ↑ Maeda TK, Sugiura D, Okazaki IM, Maruhashi T, Okazaki T (April 2019). "Atypical motifs in the cytoplasmic region of the inhibitory immune co-receptor LAG-3 inhibit T cell activation". The Journal of Biological Chemistry. 294 (15): 6017–6026. doi: 10.1074/jbc.RA119.007455 . PMC   6463702 . PMID   30760527.
  17. ↑ Zeitlmann L, Sirim P, Kremmer E, Kolanus W (March 2001). "Cloning of ACP33 as a novel intracellular ligand of CD4". The Journal of Biological Chemistry. 276 (12): 9123–9132. doi: 10.1074/jbc.M009270200 . PMID   11113139.
  18. ↑ Gorska MM, Stafford SJ, Cen O, Sur S, Alam R (February 2004). "Unc119, a novel activator of Lck/Fyn, is essential for T cell activation". The Journal of Experimental Medicine. 199 (3): 369–379. doi:10.1084/jem.20030589. PMC   2211793 . PMID   14757743.
  19. ↑ Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA (June 1998). "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody". Nature. 393 (6686): 648–659. Bibcode:1998Natur.393..648K. doi:10.1038/31405. PMC   5629912 . PMID   9641677.
  20. ↑ "Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents" (PDF). AIDSinfo. U.S. Department of Health & Human Services. 2013-02-13. Archived from the original (PDF) on 2013-10-29. Retrieved 2013-10-24.
  21. ↑ Bofill M, Janossy G, Lee CA, MacDonald-Burns D, Phillips AN, Sabin C, et al. (May 1992). "Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis". Clinical and Experimental Immunology. 88 (2): 243–252. doi:10.1111/j.1365-2249.1992.tb03068.x. PMC   1554313 . PMID   1349272.
  22. 1 2 3 4 5 HIV Medicine Association (February 2016), "Five Things Physicians and Patients Should Question", Choosing Wisely: an initiative of the ABIM Foundation , HIV Medicine Association, retrieved 9 May 2016
  23. ↑ Cooper K, Leong AS (2003). Manual of diagnostic antibodies for immunohistology. London: Greenwich Medical Media. p. 65. ISBN   1-84110-100-1.
  24. ↑ Zamani M, Tabatabaiefar MA, Mosayyebi S, Mashaghi A, Mansouri P (July 2010). "Possible association of the CD4 gene polymorphism with vitiligo in an Iranian population". Clinical and Experimental Dermatology. 35 (5): 521–524. doi:10.1111/j.1365-2230.2009.03667.x. PMID   19843086. S2CID   10427963.
  25. ↑ Ciccarelli F, De Martinis M, Ginaldi L (2014). "An update on autoinflammatory diseases". Current Medicinal Chemistry. 21 (3): 261–269. doi:10.2174/09298673113206660303. PMC   3905709 . PMID   24164192.
  26. ↑ "550280 – BD Biosciences". BD Biosciences. Becton Dickinson.

Further reading

This article incorporates text from the public domain Pfam and InterPro: IPR015274
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.