Epitopes described in "Responses against a subdominant CD8+ T cell epitope protect against immunopathology caused by a dominant epitope."

Article Authors:Tracy J Ruckwardt; Cindy Luongo; Allison M W Malloy; Jie Liu; Man Chen; Peter L Collins; Barney S Graham
Article Title:Responses against a subdominant CD8+ T cell epitope protect against immunopathology caused by a dominant epitope.
Reference Detail
Reference ID:1020907
Abstract:CD8(+) T cell responses are critical for the control of virus infections. Following infection, epitope-specific responses establish an unpredictable but reproducible pattern of dominance that is dictated by a large number of both positive and negative factors. Immunodomination, or diminution of subdominant epitope-specific responses by dominant epitopes, can play a substantial role in the establishment of epitope hierarchy. To determine the role of a dominant (K(d)M2(82-90)) and a subdominant (D(b)M(187-195)) epitope of respiratory syncytial virus in viral control and immunodomination, MHC-binding anchor residues in the two epitopes were mutated individually in recombinant infectious viruses, greatly reducing or deleting the epitope-specific CD8(+) T cell responses. Neither mutation negatively affected viral clearance in mice, and compensation by the unmutated epitope was seen in both cases, whereas compensation by five other subdominant epitopes was minimal. Mutation of the dominant K(d)M2(82-90) response resulted in effective viral clearance by the subdominant epitope with less illness, whereas mutation of the subdominant D(b)M(187-195) response resulted in overcompensation of the already dominant K(d)M2(82-90) epitope, and increased severity of illness. Increased illness was associated with poor functionality of the abundant population of CD8(+) T cells specific to the dominant K(d)M2(82-90) epitope, as measured by the percentage and magnitude of IFN- production. These data demonstrate efficient viral clearance, and a protective effect of subdominant CD8(+) T cell responses.
Reference Type:Literature
PubMed ID:20833834
Journal:J Immunol
Journal Volume:185
Article Pages:4673-80
Journal ISSN:0022-1767
Article Chemical List:Antigens, Viral;Epitopes, T-Lymphocyte;Immunodominant Epitopes
Article MeSH List:Animals; Antigens, Viral(immunology); CD8-Positive T-Lymphocytes(immunology); Epitopes, T-Lymphocyte(immunology); Female; Immunodominant Epitopes(immunology); Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Respiratory Syncytial Virus Infections(immunology); Respiratory Syncytial Viruses(immunology)
Curation Last Updated:2015-07-30 20:37:42