CD3: CHARACTERISTICS, FUNCTIONS - CHEMISTRY - 2024

CD3, in immunology, is the acronym that describes the “group of differentiation 3” (Cluster of Differentiation 3) and defines a protein complex present in the plasma membrane of cells of the immune system known as T lymphocytes.

Proteins of the CD3 complex normally associate with another protein complex on the plasma membrane of lymphocytes called the T cell receptor or TCR (T Cell Receptor).

Scheme of the reception complex in a cytotoxic T cell (CD8 +), where the presentation of the antigen in the MHC context and the formation of the TCR-CD3 complex are observed (Source: Engineer gena via Wikimedia Commons)

TCR is a heterodimer composed of two peptide chains linked together by disulfide bonds. As can be inferred from its name, TCR is unique to cells of the T lymphocyte lineage and has important implications for the immune functions of these cells.

In addition, each T cell has a specific TCR, since these proteins are actually a kind of antibody, so they are capable of recognizing only a defined type of antigen.

The proteins of the CD3 complex have transcendental functions in the transduction of signals related to the interaction between the TCR complex and its specific antigen, therefore they participate in an important part of the development of T lymphocytes known as "activation".

characteristics

CD3 is considered by many authors as a “coreceptor” complex of the T-cell receptor complex (TCR). It is a molecule that is expressed during the early stages of T lymphocyte development.

It is present in both helper T lymphocytes and cytotoxic T lymphocytes, but it has not been detected in other lymphoid cells such as B cells or natural killer cells (NKs).

Structure

The CD3 complex is a protein complex of five invariant polypeptide chains known as γ, ε, δ, ζ and η; These chains associate with each other to form three dimeric structures: the γε heterodimer, the δε heterodimer and the ζζ homodimer or the ζη heterodimer.

90% of the CD3 complexes have the ζζ homodimer, while the ζη heterodimer has been found only in the remaining 10%.

With the exception of the ζ and η chains, the peptide chains of the CD3 complex are encoded by different genes. ζ and η are encoded by the same gene, but go through different splicing processes.

Diagram of the TCR receptor complex of a CD4 lymphocyte, helper or helper. The association of TCR with the CD3 protein complex is observed. The dimeric structures that make up CD3 are also appreciated (Source: TCR_complex.jpg: Ciar (talk) at en.wikipediaTCRComplex.png: Anriarderivative work: Marek M via Wikimedia Commons)

The γ, ε and δ proteins of the CD3 complex are part of the immunoglobulin superfamily and are transmembrane proteins. They have a transmembrane domain, a cytosolic domain of more than 40 amino acids, and an extracellular domain (immunoglobulin type).

The peptide chain ζ is quite different from the other three: its extracellular portion is about 9 amino acids long, has a short transmembrane segment, and has a cytosolic domain 113 amino acids long.

Characteristics of the transmembrane portion of CD3 chains

The peptide chains of the CD3 complex have a transmembrane region that has an aspartic acid or glutamic acid residue (negatively charged residues), capable of interacting with the positive charges of the amino acids in the transmembrane portion of the TCR complex.

The co-reception function of the CD3 complex with the TCR complex is closely related to the "transmembrane" interaction of the residues of the polypeptide chains that make up both complexes.

Characteristics of the cytosolic portion of the CD3 chains

All cytosolic chains of the CD3 complex possess a tyrosine-based immunoreceptor activation motif (ITAM).

These ITAM motifs are responsible for inward signal transduction, as they interact with tyrosine kinase enzymes, which are important mediators in intracellular signaling.

Features

Knowing that CD3 is a multi-component complex, it is important to specify that it collaborates with the interaction of the antigen with the TCR receptor, but does not participate in it, that is, it does not come into contact with the antigen.

Numerous lines of evidence suggest that CD3 is not only necessary to mediate antigen-antibody interaction on the surface of T cells, but that its expression is required for the self-expression of the TCR complex.

The extracellular portion of the CD3 complex is used as an "antigen" for antibody recognition of cells of the T lymphocyte lineage, which is important from the point of view of clinical cytology and disease diagnosis.

Functions during T-cell activation

T cells or lymphocytes participate in the main phenomena of the humoral and cellular immune response, which are highly dependent on their activation and multiplication.

The CD3 molecular complex acts during T-cell activation by interacting with the TCR complex and forming the TCR-CD3 "effector" complex.

Remember that the formation of this complex will only occur once the T cell in question recognizes an antigen that is presented to it in the context of a molecule of the major histocompatibility complex or MHC (Major Histocompatibility Complex) of class I or class II, depending on the type of T lymphocyte.

The antigen-MHC / TCR complex / CD3 complex interaction triggers a complicated signaling process, which begins in the T lymphocyte membrane and ends in the cell nucleus with the stimulation of the transcription of specific genes involved in the cell cycle and differentiation..

CD3, as has been said, collaborates in the transduction of the signals, since the ITAM domains of its polypeptide chains interact with a cascade of protein tyrosine kinases that are activated, for the most part, by phosphorylation.

Tyrosine kinase enzymes "recruit" and activate other elements downstream in the signaling chain, especially some "scaffold" proteins and other enzymes with the ability to activate or induce the release of molecules that function as second messengers and transcription factors.

Immunosynapsis

As well as what occurs at the sites of interaction and exchange of signals between two neurons (neuronal synapses), the sites of interaction between cells that present antigens in the context of MHC molecules and the membrane receptors on the surface of neurons. T lymphocytes have been termed "immnosinapsis."

The CD3 complex, since it actively participates in the interaction, is an essential part of the immunosynapsis sites.

References

1. Abbas, AK, Lichtman, AH, & Pillai, S. (2014). Cellular and molecular immunology E-book. Elsevier Health Sciences.
2. Actor, JK (2019). Introductory Immunology, 2nd: Basic Concepts for Interdisciplinary Applications. Academic Press.
3. Burmester, G., & Pezzutto, A. (2003). Color Atlas of Immunology With contributions by. New York, USA: Thieme.
4. Chetty, R., & Gatter, K. (1994). CD3: structure, function, and role of immunostaining in clinical practice. The Journal of pathology, 173 (4), 303-307.
5. Kindt, TJ, Goldsby, RA, Osborne, BA, & Kuby, J. (2007). Kuby immunology. Macmillan.