CD3

Synonyms: Cluster of differentiation 3

by Assia Bassarova

Background:

The CD3 protein is a pan T-cell marker, a complex of four structurally distinct membrane glycoprotein isoforms, 20-50 kDa, comprising extracellular, transmembrane and intracellular domains. CD3 is associated with an α/β or γ/δ heterodimer creating the T-cell receptor (TCR). The TCR–CD3 complex is formed through noncovalent association of TCR with a CD3 signaling apparatus consisting of the γ, δ, ε and ζ subunits.

CD3 is found only in the T-cells and activated NK-cells. T cells are a diverse and important group of lymphocytes that mature and undergo a positive and negative selection processes in the thymus. These cells play a vital role in both components of active immunity, including cell-mediated and to some extent humoral immunity. CD3 appears in the cytoplasm of prothymocytes, and on the surface of approximately 95% of thymocytes. Cytoplasmic CD3 is lost as the cells differentiate into medullary thymocytes.

All T lymphocytes have the TCR (T-cell receptor) and the pan-T-cell co-receptor CD3. It recognizes the antigen-loaded MHC molecules on other cells.

Staining in normal tissues:

  • In all lymphoid tissues (lymph nodes, thymus, mucosa-associated lymphoid tissue of the guts, lungs) CD3 staining highlights the T-areas and shows a distinct membranous staining av virtually all T-cells.
  • Natural killer (NK) cells are lymphocytes with large granular lymphocyte morphology, CD3+/CD56+ phenotype, non-MHC-restricted cytotoxicity, and germ-line configuration T-cell receptor genes.
  • In therapy resistant celiac disease, a shift from membranous to cytoplasmic CD3 expression is seen (together with loss of CD8).

Staining in tumors:

  • In malignant lymphomas, CD3 is a pan-T-cell lineage-restricted antigen, detected in 80-97% of the T-cell lymphomas.
  • Aberrant loss of CD3 is reported in mature post-thymic T-cell lymphomas including cases of mycosis fungoides, peripheral T-cell lymphoma NOS and anaplastic large cell lymphoma.
  • NK-cell lymphomas can show a cytoplasmic CD3 staining.
  • Reed-Sternberg cells in Hodgkin disease may show a globular paranuclear reaction.
  • Aberrant CD3 expression is observed in rare cases of non-Hodgkin B-cell lymphomas.

Staining pattern: Membranous and cytoplasmic.

Control tissue: Tonsil or appendix, where virtually all T-cells in the T-cell areas, as well scattered small T-cells in the germinal centers of the secondary lymphoid follicles show a strong distinct membranous staining (Fig. 1)

Application:

  • CD3 is an important marker in the classification of malignant lymphomas and lymphoid leukaemia.
  • Also the marker is useful for the identification of T-cells in, e.g., celiac disease, lymphocytic colitis and colorectal carcinomas associated with loss of a mismatch repair protein.

Selected references: