Medical applications of leukocyte surface molecules--the CD molecules

Abstract

Leukocytes are the cells of the immune system and are centrally involved in defense against infection, in autoimmune disease, allergy, inflammation, and in organ graft rejection. Lymphomas and leukemias are malignancies of leukocytes, and the immune system is almost certainly involved in most other cancers. Each leukocyte expresses a selection of cell surface glycoproteins and glycolipids which mediate its interaction with antigen, with other components of the immune system, and with other tissues. It is therefore not surprising that the leukocyte surface molecules (CD molecules) have provided targets for diagnosis and therapy. Among the "celebrities" are CD20, a target for lymphoma therapeutic antibodies which earns $2 billion annually (and makes a significant difference to lymphoma patients), and CD4, the molecule used by the human immunodeficiency virus (HIV) as an entry portal into cells of the immune system. This short review provides a background to the CD molecules and antibodies against them, and summarizes research, diagnostic, and therapeutic applications of antibodies against these molecules.

Figure 1

Flow cytometric analysis of blood cells to count B cells, T cells, and the two major T cell sub-sets, CD4 and CD8 T cells. The upper left panel shows a plot of forward (low-angle) light scatter against side (90°) light scatter, proportional to size and internal complexity of cells respectively. This plot allows the selection of the lymphocyte population (black) from the other blood cells (gray). Subsequent panels show fluorescence signals from the lymphocytes only (“gated” on lymphocytes by dual scatter). Top right: CD19, a marker for B cells. Middle left: CD3, a marker for T cells. Middle right: dual color plot of CD3 against CD19, showing T cells, B cells, and cells which are neither T cells nor B cells, with a very small number of cells reacting with both reagents. The bottom panels show plots of CD 8a against CD8, looking at only the T cells (“gated” on CD3–positive cells, left) or all lymphocytes (gated only by dual scatter, right). CD4 and CD8 expression are seen to be largely mutually exclusive. The flow cytometer provides precise counts of the relative numbers of cells in each population.