CLA - guiding T-cells to sites of inflammation

Fri, 08/14/2015 - 09:05

T-cells infiltrating sites of inflammation of the skin typically express the cutaneous lymphocyte-associate antigen (CLA). This antigen is defined by the binding of the monoclonal CLA antibody HECA-452. The CLA antigen is a fucose-containing oligosaccharide and is found on many of the ligands that are recognized by the adhesion proteins P-selectin and E-selectin. CLA is primarily expressed by memory T-cells. Homing of memory T-cells to sites of inflammation is mediated by the adhesion of CLA coated proteins to vascular endothelial cells expressing P-and E-selectins. Early studies of P- and E-selectin binding to glycoprotein ligands revealed the importance of CLA coating for ligand binding. Borges et al. used the HECA-452 CLA antibody to show PSGL-1 exists in two forms, one with CLA and the other without (1). CLA modification allowed PSGL-1 to bind to E-selectin while the other was specific for P-selectin. This finding was an important demonstration of the functional relevance of CLA modification in homing of T-cells. CLA-positive T-cells are found in healthy and diseased skin but are typically enriched at the latter, for example at psoriasis lesions. Understanding of CLA will provide a deeper understanding of skin inflammation mechanisms and may provide strategies for therapeutic treatment of certain skin disorders. A study from Brigham and Women’s hospital by the Kupper group elucidated the mechanism of vitamins A and D treatment of skin diseases (2). They used the CLA antibody in western blotting experiments to demonstrate vitamins A or D treatment down regulates expression of CLA. This provides a rationale for the efficacy of these compounds for treatment of various skin disorders. Defining cell types by glycoprotein expression is an important method of characterizing cell populations. In addition to characterization of cells using the HECA-452 CLA antibody, Walcheck et al. sought to identify monoclonal antibodies to characterize cells expressing other oligosaccharide antigens of biological relevance (3). This study identified the monoclonal CHO-131 antibody as an important tool to further classify subsets of T-cells that are recognized by the CLA antibody. Measuring T-cell infiltration is an excellent marker of inflammation and can provide a convenient assay of drug efficacy. Kim et al. used the CLA antibody for immunofluorescence to examine synergistic effects of drug treatments on a mouse model of dermatitis (4). By showing a lack of CLA-positive T-cells, their study demonstrated the efficacy of drug combinations to improve treatment of dermatitis.


  1. 9353350
  2. 17910894
  3. 12010808
  4. 22023698

Blog Topics