Control of murine cytomegalovirus in the lungs: relative but not absolute immunodominance of the immediate-early 1 nonapeptide during the antiviral cytolytic T-lymphocyte response in pulmonary infiltrates.
The lungs are a major organ site of cytomegalovirus (CMV) infection, pathogenesis, and latency. Interstitial CMV pneumonia represents a critical manifestation of CMV disease, in particular in recipients of bone marrow transplantation (BMT). We have employed a murine model for studying the immune response to CMV in the lungs in the specific scenario of immune reconstitution after syngeneic BMT. Control of pulmonary infection was associated with a vigorous infiltration of the lungs, which was characterized by a preferential recruitment and massive expansion of the CD8 subset of alpha/beta T cells. The infiltrate provided a microenvironment in which the CD8 T cells differentiated into mature effector cells, that is, into functionally active cytolytic T lymphocytes (CTL). This gave us the opportunity for an ex vivo testing of the antigen specificities of CTL present at a relevant organ site of viral pathogenesis. The contribution of the previously identified immediate-early 1 (IE1) nonapeptide of murine CMV was evaluated by comparison with the CD3epsilon-redirected cytolytic activity used as a measure of the overall CTL response in the lungs. The IE1 peptide was detected by pulmonary CTL, but it accounted for a minor part of the response. Interestingly, no additional viral or virus-induced antigenic peptides were detectable among naturally processed peptides derived from infected lungs, even though infected fibroblasts were recognized in a major histocompatibility complex-restricted manner. We conclude that the antiviral pulmonary immune response is a collaborative function that involves many antigenic peptides, among which the IE1 peptide is immunodominant in a relative sense.
Holtappels
R
R
Institute for Virology, Johannes Gutenberg-University, 55101 Mainz, Germany.
Podlech
J
J
Geginat
G
G
Steffens
H P
HP
Thomas
D
D
Reddehase
M J
MJ
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology*; D017874:Immediate-Early Proteins / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology*; D007700:Kinetics; D008168:Lung / Q000166:cytology / Q000276:immunology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D015534:Trans-Activators / Q000276:immunology*; D014779:Virus Replication
C094775:IE-1 protein, murine cytomegalovirus; D017874:Immediate-Early Proteins; D016056:Immunodominant Epitopes; D015534:Trans-Activators