Eg. Pamer et al., MHC CLASS-I ANTIGEN-PROCESSING OF LISTERIA-MONOCYTOGENES PROTEINS - IMPLICATIONS FOR DOMINANT AND SUBDOMINANT CTL RESPONSES, Immunological reviews, 158, 1997, pp. 129-136
Listeria monocytogenes (L. monocytogenes) secretes proteins associated
with its virulence into the cytosol of infected cells. These secreted
proteins are degraded by host cell proteasomes and processed into pep
tides that are bound by MHC class I molecules in the endoplasmic retic
ulum. We have found that the MHC class I antigen-processing pathway is
very efficient at generating the epitopes that are presented to cytol
ytic T lymphocytes (CTL). Depending on which antigen is investigated,
from 3 to 30 % of degraded antigens are processed into nonamer peptide
s that are bound by MHC class I molecules. Surprisingly, neither the e
fficiency of epitope generation nor the absolute number of epitopes pe
r infected cell determines the magnitude of the in vivo CTL response.
One of the least prevalent epitopes, derived from an antigen that is v
irtually undetectable in infected cells, primes the immunodominant Cn.
response in L. monocytogenes-infected mice. Our studies suggest that
immunodominant and subdominant T-cell responses cannot be predicted by
the prevalence of antigens or epitopes alone, and that additional fac
tors, yet to be determined, are involved.