Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR β chain: A means for graft rejection and immunosuppression

A peptide (Leu-Gly-Arg-Pro-Asp-Glu-Asp-Ser-Ser-Ser-Ser-Ser-Ser-Ser-Cys) that was identical to residues 82 through 96 of a predicted protein of 208 amino acids from the immediate-early region (IE-2) nucleic acid sequence of human cytomegalovirus was chemically synthesized. By computer analysis, the first five amino acids of this peptide showed sequence homology to the β chain of the human histocompatibility complex HLA-DR. The homologous amino acids, 53 through 57, were located in a region that is conserved between the human DR β chain and the β chain of the H-2 class II histocompatibility antigen for mice. The shared region between the IE-2 protein and DR β chain were similar in both hydrophilicity and predicted β-turn potential. The IE-2 viral peptide induced antibodies that specifically recognized the human DR β chain. These observations describe a protein encoded by the IE-2 region of human cytomegalovirus that contains sequence homology and shows immunologic cross-reactivity with a conserved domain of HLA-DR and suggest a mechanism to explain how human cytomegalovirus infection contributes to graft rejection after transplantation.