Principles of cytomegalovirus antigen presentation in vitro and in vivo

Cytomegaloviruses are members of the ubiquitous family of herpesviruses. They escape immunological clearance and persist throughout life in the infected host. Yet, the stability of the balance of this virus-host interaction is dependent upon the state of the cellular immune response, and usually requires the function of specific CD8 T lymphocytes. In a mouse model, the major antigen that triggers protective CD8 T lymphocytes has been characterized as a nonameric amino acid motif of a nonstructural virus protein. Analysis of the naturally presented peptide has led to the conclusion that the sequence of an antigenic epitope is not the only parameter that decides upon its efficient presentation. Furthermore, the virus has developed regulatory functions that can prevent antigen presentation in productively infected cells. Contradictions between in vivo and in vitro findings are resolved in a hypothesis postulating an essential contribution of cytokines to the in vivo control of productive cytomegalovirus infection.