Human Leukocyte Antigen (HLA) part 78

Downregulation or complete loss of HLA class I gene expression has been reported in variety of human solid and haematopoetic maligancies such as melanoma, colorectal, breast, lung and cervical carcinoma, and these changes were ranged from 3,4% to 60% depending on the tumour subtype analysed. In addition, loss of heterozygosity at the HLA loci is a frequent event in some tumour entities-like colorectal carcinoma and melanoma, but not in others, like renal cell carcinoma and could therefore contribute to the downregulate of HLA class I antigens in selected tumours types. The molecular mechanisms leading to defects in the HLA class I antigen presentation pathway have been well characterized upon viral infections. The human cytomegalovirus represents one suitable model for viral interference with the HLA class I antigen presentation pathway. For example,  the human cytomegalovirus encodes at least four proteins that impair the antigen-processing pathway at different steps from proteosomal degradation to peptide transport, formation of the trimeric HLA class I HC/β2 m/peptide complex to its transport to the cell surface. Furthermore, many other viruses also interfere with the HLA class I APM.