Surface proteins and glycoproteins of human leucocytes.

The essential condition for understanding the function of the immune system is to know as completely as possible its components, their properties, functions and mutual relations on a molecular level. That is, the first necessary step is to do a basic 'inventory' of all parts of the system. One of the most active areas in this respect is the investigation of surface macromolecules of leucocytes. Many leucocyte surface components have been identified, mostly with the aid of monoclonal antibodies, including such important molecules as various receptors and cell adhesion molecules. The final goal of these efforts is to identify and functionally define all surface components of all types of leucocytes. It is not clear how close to this ideal we are now, but it seems likely that many, perhaps most, of the leucocyte membrane proteins and glycoproteins are yet to be discovered. In the present review we attempt to summarize the information available on the surface components of human leucocytes identified so far. Because of space limitations and enormous extent of the field to be covered, we had to restrict the discussion only to the structurally and functionally best known and most interesting molecules. Also, we had to keep the number of citations to a minimum of those most recent and most relevant and wherever possible we cite detailed reviews on individual molecules. We apologize to the authors of all papers not cited for this reason. The Tables attached contain basic information on most human leucocyte surface antigens* for which at least a minimum of biochemical data (Mr) is available. For the sake of clarity, we grouped all these antigens in Tables according to their prevalent expression on different cell types [i.e. antigens ofT lymphocytes, B lymphocytes, NK (natural killer) cells, myeloid cells (monocytes, macrophages and granulocytes) and finally antigens with broader expression]. We are aware that our classification is sometimes rather arbitrary, but, strictly speaking, there are very few molecules expressed absolutely specifically on a certain leucocyte subpopulation and most antigens should be in fact classified as 'lineage non-specific'. In this review we use as much as possible the 'CD nomenclature' of the International Workshops on Human Leucocyte Differentiation Antigens (Bernard et al., 1984a; Reinherz et al., 1986; McMichael et al., 1987), which greatly clarifies certain confusion due to using different arbitrary names by different authors for identical molecules. Thus, in the text we concentrate more on functional aspects, relations between various membrane molecules etc., while descriptive facts on Mr values, expression and nomenclature can be found mostly in the Tables. Antigen-specific receptors and functionally related molecules Recognition of substances foreign to an organism is the basis of immune response. The recognition is accomplished by soluble recognition molecules, i.e. immunoglobulins, and by membrane-bound antigenspecific receptors. There are basically two kinds of these receptors: membrane immunoglobulins ofB lymphocytes and so called T cell antigen receptors of T lymphocytes. These are some similarities but also important differences between these two systems. Membrane-bound immunoglobulins are structurally very similar to the secreted soluble immunoglobulins, except for a C-terminal hydrophobic stretch of amino acids in the heavy chain which serves to anchor the molecule in the lipid membrane ofB lymphocytes (Rogers et al., 1980). The membrane-bound immunoglobulins are mostly of IgM and IgD isotype; essentially nothing is known about possible functional differences between these isotypes but apparently both murine mIgM and mIgD (as well as mIgG) can act as signal transmission molecules (Mizuguchi et al., 1986). Structure, mechanisms of generation of binding sites diversity and molecular genetics of immunoglobulins have been subjects of numerous reviews and therefore need not be discussed here. Each B lymphocyte clone carries mlgs of unique structure of combining site and thus exhibits unique antigen specificity. Recognition of the respective antigen by this surface receptor provides a signal necessary for activation of the B lymphocyte, its clonal expansion and terminal differentiation into either memory B cells or plasma cells, which secrete soluble immunoglobulin of structure and specificity identical with or very similar to that of the mlg on the originally stimulated B lymphocyte (somatic mutations during this proliferation/differentiation process can alter affinity and fine specificity of the resulting immunoglobulins). The biochemical basis of transmembrane signalling through mIg was thoroughly reviewed by Cambier et al. (1987a); it involves the second messenger system based on hydrolysis of phosphatidylinositol bisphosphate, rise of intracytoplasmic Ca2l concentration and activation of protein kinase C. In most cases further 'helper' signals are necessary in addition to the primary signal provided by the antigen-mIg interaction to achieve proliferation and terminal differentiation of the B lymphocytes. These secondary signals are provided by lymphokines secreted mostly by helper T lymphocytes. Which of these second signals are necessary and sufficient under physiological conditions (and in which order) is not exactly known, but in vitro interleukins 1, 2, 4, 5 and 6, and IgE, C3d and probably also other factors, were shown to enhance B