**2.1. HLA Class I antigens**

The cell surface glycopeptide antigens of the HLA A, B and C series are called HLA Class I anti‐ gens [2]. HLA Class I antigens are expressed on all nucleated cells of the body. Additionally, they are found in soluble form in plasma and adsorbed onto the surface of platelets. Erythrocytes also adsorb HLA Class I antigens to varying degrees depending on the specificity (e.g. HLA-B7, A28 and B57 are recognizable on erythrocytes as so called "Bg" antigens). Immunological studies in‐ dicate that HLA-B (which is also the most polymorphic) is the most significant HLA Class I locus, followed by HLA-A and then HLA-C. There are other HLA Class I loci (e.g. HLA E, F, G, H, J, K and L), but most of these may not be important as loci for "peptide presenters".

The HLA Class I antigens comprise a 45 Kilodalton (Kd) glycopeptide heavy chain with three domains, which is non-covalently associated with β2-microglobulin, which plays an important role in the structural support of the heavy chain [3]. The HLA Class I molecule is assembled inside the cell and ultimately sits on the cell surface with a section inserted into the lipid bilayer of the cell membrane and has a short cytoplasmic tail.

The general structure of HLA Class I, HLA Class II and IgM molecules show such similarity of subunits, that a common link between HLA and immunoglobulins, back to some primordial cell surface receptor is likely. The full 3-dimensional structure of HLA-A Class I molecules has been determined from X-ray crystallography [4]. This has demonstrated that the molecule has a cleft on its outermost surface, which holds a peptide. Consequently, if a cell becomes infected with a virus, the virally induced proteins within the cell are broken down into small peptides which are then inserted into this cleft during the synthesis of HLA Class I molecules. The HLA Class I molecules then translocate these virally (or self) induced peptides to the cell surface leading to activation of cytotoxic (CD8) T cells [5]. This role of HLA Class I, in identifying cells, which are changed (e.g. virally infected), is the basis for their expression on all cells [4]. Epitopes on certain expressed HLA Class I molecules also act as ligands for killer inhibitory receptors expressed on natural killer [6] cells, thereby influencing NK cell function [7].

### **2.2. HLA class II antigens**

The cell surface glycopeptide antigens of the HLA DR, DP and DQ loci are termed HLA Class II [1]. The tissue distribution of HLA Class II antigens is confined to the "immune competent" cells, including B-lymphocytes, macrophages, and endothelial cells and activated T-lympho‐ cytes. The expression of HLA Class II, on cells, which would not normally express them, is stimulated by cytokines like interferon-γ and is associated with acute graft rejection in the setting of transplantation. HLA Class II molecules consist of two chains each encoded by genes in the "HLA Complex" on Chromosome 6 [3]. The T Cells, which link to the HLA Class II molecules, are Helper (CD4) T cells. This role of HLA Class II, in initiating a general immune response, is the rationale for their limited expression on "immunologically active" cells (B lymphocytes, macrophages, etc.) and not on all tissues [4].
