Purification and Properties of p 103, a Novel 103-kDa Component of Postsynaptic Densities

A 103-kDa protein present in membrane cytoskeletal preparations from bovine brain has been identified. We have purified this protein to greater than 95% homogeneity using gel filtration and ion-exchange chromatography. This protein, p103, is an asymmetric dimer in dilute solution and has two major variants that can be distinguished by isoelectric focussing, pI 5.60 and 5.75. Using subcellular fractionation, it is most enriched in postsynaptic densities. Immunolocalization with anti-p103-specific antibodies reveals that it is confined to the dendrites and perikarya; it is apparently absent from spinal cord axons. It coextracts from brain membrane-skeletal preparations with brain spectrin and actin, but in vitro, it does not interact with them.     

HLA and disease.

Many human diseases are associated with HLA class I, class II and class III antigens. It appears that the class III antigen disease associations can be explained by a direct defect operating at the level of either the class III gene or its gene product. The mechanism underlying class I and class II antigen disease associations is at present unknown. In this review we have considered thirty diseases which have been ranked according to their relative risk as defined by the frequency of a given HLA antigen in patient and control populations. The chronic inflammatory disorder, ankylosing spondylitis and its association with HLA B27 has been used as a model to study the HLA linked diseases. We have suggested that the disease may be caused by the Gram-negative microorganism Klebsiella which has antigenic similarity to HLA B27. It is proposed that some antibodies made against Klebsiella bind to HLA B27, thereby acting as autoantibodies leading to the pathological sequelae of chronic inflammatory arthritis. This is the crosstolerance hypothesis or molecular mimicry model and it has been compared to the receptor model. It is further suggested that the crosstolerance hypothesis can be utilised as a general theory to explain the association of other diseases with the class I and class II antigens, and offer a possible explanation for the polymorphism of HLA.