CD3

Characteristics

The CD3 protein is a 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 CD3 complex is responsible for mediating signal transduction to the internal environment upon antigenic recognition by TCR, causing T-cell proliferation and release of cytokines. Except for a weak expression in Purkinje cells (with some of the Abs) and activated NK-cells, CD3 is found only in T-cells. CD3 appear in the cytoplasm of prothymocytes, and on the surface of about 95% of thymocytes, while cytoplasmic CD3 is lost as the cells differentiate into medullary thymocytes.

In therapy resistant celiac disease, a shift from membranous to cytoplasmic CD3 expression is seen (together with loss of CD8).

Neoplasms

In malignant lymphomas, CD3 is a pan-T-cell lineage-restricted antigen, detected in 80-97% of the T-cell lymphomas. Mature T-cell lymphomas including cases of mycosis fungoides, peripheral T-cell lymphoma and anaplastic large cell lymphoma may aberrantly lose CD3. NK-cell lymphomas can show a cytoplasmic reaction. Reed-Sternberg cells may show a globular paranuclear reaction.

Application

CD3 is an important marker in the classification of malignant lymphomas and lymphoid leukaemias.

Also the marker is useful for the identification of T-cells in, e.g., celiac disease, lymphocytic colitis (Fig 1A) and colorectal carcinomas associated with loss of a mismatch repair protein (Fig 1B).

Visualization

Several well performing Abs for formalin fixed tissue are available, e.g., clone F7.2.38, clone PS1, clone (rabbit) SP7, clone UCHL1, pAb A0452 (Dako), and pAb RB-360 (Neomarkers). An efficient HIER is mandatory for the detection of CD3 in paraffin sections. Some pAbs stain thymus epithelial cells, others cross react with mesothelial cells. The epitope reactivity may diminish in slides stored at room temperature.

Control: Appendix or tonsil. The T-cells should stain as intensely as possible without reaction of the B-cells. A good stain quality indicator is the germinal centres, in which the isolated T-cells should be distinctively labelled without any reaction in the B-cells.

Assessments

Run 5 2001

Run 14 2005

Run 22 2008

Selected references

Chadburn A, Knowles DM. Paraffin-resistant antigens detectable by antibodies L26 and polyclonal CD3 predict the B- or T-cell lineage of 95% of diffuse aggressive non-Hodgkin's lymphomas. Am J Clin Pathol. 1994 Sep;102(3):284-91.

Chetty R, Gatter K. CD3: structure, function, and role of immunostaining in clinical practice. J Pathol. 1994 Aug;173(4):303-7.

Jones M, Cordell JL, Beyers AD, Tse AG, Mason DY. Detection of T and B cells in many animal species using cross-reactive anti-peptide antibodies. J Immunol. 1993 Jun 15;150(12):5429-35.

Kurtin PJ, Roche PC. Immunoperoxidase staining of non-Hodgkin's lymphomas for T-cell lineage associated antigens in paraffin sections. Comparison of the  performance characteristics of four commercially available antibody preparations. Am J Surg Pathol. 1993 Sep;17(9):898-904.

Steward M, Bishop R, Piggott NH, Milton ID, Angus B, Horne CH. Production and characterization of a new monoclonal antibody effective in recognizing the CD3 T-cell associated antigen in formalin-fixed embedded tissue. Histopathology. 1997 Jan;30(1):16-22.