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Beirne B. Carter Center for Immunology Research and
Department of Pathology and Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908
Beirne B. Carter Center for Immunology Research and
Department of Pathology and Microbiology, University of Virginia Health Sciences Center, Charlottesville, VA 22908
CTL play a major role in the clearance of respiratory syncytial
virus (RSV) during experimental pulmonary infection. The fusion (F)
glycoprotein of RSV is a protective Ag that elicits CTL and Ab response
against RSV infection in BALB/c mice. We used the strategy of screening
a panel of overlapping synthetic peptides corresponding to the RSV F
protein and identified an immunodominant H-2Kd-restricted
epitope (F85–93; KYKNAVTEL) recognized by CD8+
T cells from BALB/c mice. We enumerated the F-specific CD8+
T cell response in the lungs of infected mice by flow cytometry using
tetramer staining and intracellular cytokine synthesis. During primary
infection, F85–93-specific effector CD8+ T
cells constitute 
4.8% of pulmonary CD8+ T cells at the
peak of the primary response (day 8), whereas matrix 2-specific
CD8+ T cells constituted 50% of the responding
CD8+ T cell population in the lungs. When RSV F-immune mice
undergo a challenge RSV infection, the F-specific CD8+ T
cell response is accelerated and dominates, whereas the primary
response to the matrix 2 epitope in the lungs is reduced by 20-fold.
In addition, we found that activated F-specific effector
CD8+ T cells isolated from the lungs of RSV-infected mice
exhibited a lower than expected frequency of IFN-
-producing
CD8+ T cells and were significantly impaired in ex vivo
cytolytic activity compared with competent F-specific effector
CD8+ T cells generated in vitro. The significance of these
results for the regulation of the CD8+ T cell response to
RSV is discussed.
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