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 ?/? or ?/? 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).


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.


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 and colorectal carcinomas associated with loss of a mismatch repair protein.


Tonsil and appendix are recommendable tissue controls for CD3. Both aggregated T-cells in the interfollicular areas and dispersed T-cells in the mantle zone and within the germinal centers must show a moderate to strong distinct membranous staining reaction, while B-cells must be negative. In the appendix a moderate to strong and distinct predominantly membranous staining reaction of the intra-epithelial T-cells should be seen without cytoplasmic staining of the columnar epithelial cells or plasma cells. 

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.

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