CD99

CD99 Full Name

CD99 molecule

CD99 Introduction

CD99 (also known as MIC2) is a highly O-glycosylated transmembrane glycoprotein that plays a unique role in cell adhesion and immune surveillance. It is encoded by a gene located in the pseudoautosomal regions (PAR1) of the X and Y chromosomes, meaning it escapes X-inactivation. Structurally, CD99 is relatively small (32 kDa) and presents as two distinct isoforms due to alternative splicing, with the extracellular domain forming a rigid, rod-like structure essential for its function.

Physiologically, CD99 functions as a critical regulator of leukocyte transendothelial migration (TEM). It acts as a "zipper" between endothelial cells; during an immune response, CD99 on the surface of white blood cells interacts with CD99 on the endothelial junctions to facilitate the passage of leukocytes from the blood into tissues (diapedesis). Beyond migration, CD99 signaling is context-dependent: in immature thymocytes (T-cells), its ligation induces apoptosis, serving as a quality control mechanism, whereas in other contexts, it promotes cell adhesion and arrests differentiation.

Figure 1. CD99 role in diapedesis. (Source: Manara MC, et al. 2025)

The clinical notoriety of CD99 stems from its status as the gold-standard diagnostic biomarker for Ewing Sarcoma. Nearly all cases of Ewing Sarcoma family tumors exhibit strong, diffuse, membranous expression of CD99. While the protein is not the genetic cause of the cancer (which is usually the EWS-FLI1 fusion), it is essential for the tumor's malignancy; silencing CD99 in these cells reduces their ability to grow and metastasize. Additionally, CD99 is relevant in hematological malignancies. It is highly expressed in T-cell Acute Lymphoblastic Leukemia (T-ALL) and Lymphoblastic Lymphoma, where it serves as a target for antibody-based therapies currently under investigation. Conversely, the loss of CD99 expression on T-cells has been observed in Hodgkin Lymphoma, suggesting a mechanism for immune evasion in that specific context.

Alternate Names for CD99

CD99; CD99 molecule; MIC2; HBA71; MIC2X; MIC2Y; MSK5X; CD99 antigen; E2 antigen; surface antigen MIC2; T-cell surface glycoprotein E2; MIC2 (monoclonal antibody 12E7); antigen identified by monoclonal 12E7, Y homolog; antigen identified by monoclonal antibodies 12E7, F21 and O13;

• Immunohistochemistry Antibodies for Pathology
• Immunohistochemistry Antibodies for Pathology

• 1. Manara MC, et al. CD99: A Key Regulator in Immune Response and Tumor Microenvironment. Biomolecules. 2025 Apr 28;15(5):632.
  2. Pasello M, et al. CD99 at the crossroads of physiology and pathology. J Cell Commun Signal. 2018 Mar;12(1):55-68.