ANTIGEN-PROCESSING BY PROTEASOMES - INSIGHTS INTO THE MOLECULAR-BASISOF CRYPTICITY

Eight to eleven amino acid residues are the sizes of predominant pepti des found to be associated with MHC class I molecules. Proteasomes hav e been implicated in antigen processing and generation of such peptide s. Advanced methodologies in peptide elution together with sequence de termination have led to the characterisation of MHC class I binding mo tifs. More recently, screening of random peptide phage display librari es and synthetic combinatorial peptide libraries have also been succes sfully used. This has led to the development and use of predictive alg orithms to screen antigens for potential CTL epitopes. Not all predict ed epitopes will be generated in vivo and the emerging picture suggest s differential presentation of predicted CTL epitopes ranging from cry ptic to immunodominant. The scope of this review is to discuss antigen processing by proteasomes, and to put forward a hypothesis that the m olecular basis of immunogenicity can be a function of proteasomal proc essing. This may explain how pathogens and tumours are able to escape immunosurveillance by altering sequences required by proteasomes for e pitope generation.