Antiviral cytotoxic T cells cross-reactively recognize disparate peptide determinants from related viruses but ignore more similar self- and foreign determinants
M. Regner et al., Antiviral cytotoxic T cells cross-reactively recognize disparate peptide determinants from related viruses but ignore more similar self- and foreign determinants, J IMMUNOL, 166(6), 2001, pp. 3820-3828
We have investigated the reactivities of cytotoxic T (Tc) cells against the
two immunodominant, H-2K(k)-restricted determinants from the:Flavivirus Mu
rray Valley encephalitis virus (MVE), MVE1785 (REHSGNEI) and MVE1971 (DEGEG
RVI). The respective Tc cell:populations cross-reactively lysed target cell
s pulsed with determinants from the MVE1785- and MVE1971-corresponding posi
tions of six other flaviviruses, despite low sequence homology in some case
s. Notably, anti-MVE1785 Tc cells recognized a determinant (TDGEERVI) that
shares with the determinant used for stimulation only the carboxyl-terminal
amino acid residue, one of two B-2K(k) anchor residues. These reactivity p
atterns were also observed in peptide-dependent IFN-gamma production and th
e requirements for in vitro restimulation of memory Te cells. However, the
broad cross-reactivity appeared to he limited to MVE-virus-derived determin
ants, as none of a range of determinants from endogenous mouse-derived sequ
ences, similar to the MVE-determinants, were recognized. Neither mere cells
infected with a number of unrelated viruses recognized. These results rais
e the paradox that virus-immune Tc cell responses, which are mostly directe
d against only a few "immunodominant" viral determinants, are remarkably pe
ptide cross-reactive.