Differentiation antigens

Leukocyte differentiation antigens provide markers for different lymphoid cell types, define cell lineages and mediate crucial leukocyte-specific functions. From serological, biochemical, structural and functional homologies, many of the antigens have been grouped into clusters of differentiation (CD), and some CD genes are polymorphic or oligomorphic, while others are monomorphic.

The CD antigen clusters are involved in numerous functions. Some examples are given below.

Accessory functions:

1. Interaction with MHC antigens leading to T cell activation: CD3 associates with a[3 TCR on CD4+ and CD8+ T cells, and the complex binds to MHC antigens along with antigenic peptides.

2. Activation of T cells requires a second signal that is delivered by the interaction of CD80(B-7)/CD28 and B cells via CD40/CD40-ligand molecules.

3. Signal transduction: Thy 1 (CDw90) is a signal transduction molecule that plays a role in T cell activation through the TCR/CD3 complex. CD19 and CD21 are involved in signal transduction in B cell activation.

4. Cell adhesion (integrins and their ligands): involves cell-cell or cell-tissue interactions during microbial infections, inflammation, tumor formation, metastasis and neural development. For example, the antigen-presenting cells (APC) and CD4+ T cells are brought into close contact by interaction between LFA-l(CDlla/CD18) antigen on the T cells with its ligands ICAM-1 and ICAM-2 on the APC and also by interaction between LFA-3 (CD58) and its counterpart CD2 on the T cells.

Markers for different cell types: T cells (CD3), MHC class Il-restricted T cells (CD4), MHC class I-restricted T cells (CD8), activated T and B cells (CD95), B cell lineage (CD19, CD20) and granulocytes (CD66).

Receptors for soluble molecules: Interleukins (CD25, CD121 through CDwl30); Fc portion of IgG (CD 16: Fc7 RIII; CD32: Fc7 RII; CD64: Fc7 RI) or IgF (CD23) and complement C3d (CD21).

Viral receptors: Human immunodeficiency virus (CD4); and Epstein-Barr virus (CD21 on B cells).

Enzymatic activity: CD10, CD13, CD26 (dipeptidylpeptidase IV); CD4.5 (phosphotyrosinc phosphatase) and CD73 (ecto-5'nucleotidase).

Ion channels: CD20 forms ion channels and functions during receptor-mediated events.

Disease associations and clinical use: A few examples: defective CD43 expression on T cells with X-chromosome-linked Wiskott-Aldrich syndrome; some minor GPI (glycosyl-phosphatidylinositol)-anchored antigens (e.g. CD55, CD58, CD59) are deficient on the red blood cells from patients with paroxysmal nocturnal hemoglobinuria (PNH). Anti-CD^ antibodies are used to treat leukemias and lymphoma and anti-CD3 antibodies to treat renal, hepatic and cardiac allograft rejection.

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