G. Weidt et al., RELATIONSHIP AMONG IMMUNODOMINANCE OF SINGLE CD8(-CELL EPITOPES, VIRUS LOAD, AND KINETICS OF PRIMARY ANTIVIRAL CTL RESPONSE() T), The Journal of immunology, 160(6), 1998, pp. 2923-2931
The primary CTL response of BALB/c mice infected with the lymphocytic
choriomeningitis (LCM) virus strain WE is directed exclusively against
one major epitope, n118, whereas a viral variant, ESC, that does not
express n118 induces CTL against minor epitopes, We identified one min
or epitope, g283, that induces primary lytic activity in ESC-infected
mice, Infections of mice with WE and ESC were used to study the hierar
chical control of a T cell response, Presentation of minor epitopes is
not reduced in WE-infected cells, Generation of CTL against n118 does
not suppress the generation of minor epitope-specific CTL systemicall
y, as mice coinfected with WE and ESC developed CTL against n118 and g
283, However, elimination of ESC and development of minor epitope-spec
ific CTL in ESC infection were slower than elimination of WE and devel
opment of CTL against n118, CD8(+) T cells against the minor epitope w
ere activated in ESC and WE infection, but did not expand in the latte
r to show lytic activity in a primary response, We explain the absence
of minor epitope-specific lytic activity in WE infection by the fast
reduction of virus load due to the early developing n118-specific CTL,
Immunodominance of CTL epitopes in primary virus infections thus can
be explained as a kinetic phenomenon composed of 1) expansion of CD8() T cells specific for individual epitopes, 2) stimulatory effect of v
irus load, and 3) negative feedback control on virus load by the faste
st CTL population.