Tolerance

6.1. Autoantigens

The fundamental study of any autoimmune disease is initiated by attempts to characterize and define the autoantigen towards which the autoantibody is directed. Research in this field is headed by immunohis-tochemical studies of recombinant proteins obtained by screening expression libraries with autoantibodies. Examples of autoantigens detected by this method consist of myelin basic protein (MBP) in mice and acetylcholine receptors in patients with myasthenia gravis.

The role of autoantigen recognition has been exemplified in a classic study by which sera from diabetic children were found to contain elevated titers of antibodies, specific for A-17 residue bovine serum peptide differing in sequence from that of human albumin. Cross-reaction of these antibodies with the p-69 (a pancreatic yS-cell surface protein) which is considered the target autoantigen in autoimmune diabetes, had been noticed [24].

It should be emphasized that even the most highly conserved and basic self structures can potentially induce autoantibody production. As such, immunizing rabbits with cytochrome C resulted in the production of antibodies against mouse specific domains of the enzyme as well as against rabbit cytochrome C. The latter was shown to react with conserved residues found in all mammalian cytochromes C [25].

6.2. Aberrant Expression of HLA

HLA are classified to two groups (I and II) based on structural and functional attributes. These antigens are characterized by a wide variance between unrelated individuals (allotypic polymorphism). Class I antigens are located in chromosome 6 and consist of three subclasses (HLA A, B and C). These molecules are found in membranes of nucleated cells and blood platelets. Class II molecules are mainly detected on macrophages, dendritic cells and other antigen pre-

Table 4. Biologie and physiologic functions of natural autoantibodies

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