Relationship among immunodominance of single CD8+ T cell epitopes, virus load, and kinetics of primary antiviral CTL response.
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 minor epitope, g283, that induces primary lytic activity in ESC-infected mice. Infections of mice with WE and ESC were used to study the hierarchical 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 systemically, as mice coinfected with WE and ESC developed CTL against n118 and g283. However, elimination of ESC and development of minor epitope-specific CTL in ESC infection were slower than elimination of WE and development of CTL against n118. CD8+ T cells against the minor epitope were activated in ESC and WE infection, but did not expand in the latter 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 virus load, and 3) negative feedback control on virus load by the fastest CTL population.
Weidt
G
G
Heinrich Pette Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany. weidt@uke.uni-hamburg.de
Utermöhlen
O
O
Heukeshoven
J
J
Lehmann-Grube
F
F
Deppert
W
W
D000818:Animals; D018984:Epitopes, T-Lymphocyte; D005260:Female; D006183:H-2 Antigens / Q000235:genetics; D007700:Kinetics; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D014764:Viral Proteins