CTL response compensation for the loss of an immunodominant class I-restricted HSV-1 determinant.
The T-cell response to even complex pathogens is often focused on only a handful of immunodominant determinants. Such narrow responses provoke a selective pressure that can drive the emergence of CTL escape variants, raising the question of whether a broader response, targeting multiple non-dominant peptides may be more beneficial. To examine the ability of the T-cell repertoire to respond to non-dominant determinants, we have investigated how mutating the dominant peptide in HSV affects the magnitude of the CD8+ T-cell response. We found that the CTL response to HSV lacking the dominant peptide was only modestly reduced compared with the wild-type virus and, surprisingly, this compensation occurred without any enhancement in the response to an established minor epitope. These findings are supportive of a malleable T-cell repertoire that can elicit strong responses to alternate, unknown determinants in the absence of the dominant response.
Stock
Angus T
AT
Department of Microbiology and Immunology, The University of Melbourne, Melbourne, Australia.
Jones
Claerwen M
CM
Heath
William R
WR
Carbone
Francis R
FR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D016056:Immunodominant Epitopes / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication
D016056:Immunodominant Epitopes; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus