Private specificities of CD8 T cell responses control patterns of heterologous immunity.
CD8 T cell cross-reactivity between viruses can play roles in protective heterologous immunity and damaging immunopathology. This cross-reactivity is sometimes predictable, such as between lymphocytic choriomeningitis virus (LCMV) and Pichinde virus, where cross-reactive epitopes share six out of eight amino acids. Here, however, we demonstrate more subtle and less predictable cross-reactivity between LCMV and the unrelated vaccinia virus (VV). Epitope-specific T cell receptor usage differed between individual LCMV-infected C57BL/6 mice, even though the mice had similar epitope-specific T cell hierarchies. LCMV-immune mice challenged with VV showed variations, albeit in a distinct hierarchy, in proliferative expansions of and down-regulation of IL-7Ralpha by T cells specific to different LCMV epitopes. T cell responses to a VV-encoded epitope that is cross-reactive with LCMV fluctuated greatly in VV-infected LCMV-immune mice. Adoptive transfers of splenocytes from individual LCMV-immune donors resulted in nearly identical VV-induced responses in each of several recipients, but responses differed depending on the donor. This indicates that the specificities of T cell responses that are not shared between individuals may influence cross-reactivity with other antigens and play roles in heterologous immunity upon encounter with another pathogen. This variability in cross-reactive T cell expansion that is unique to the individual may underlie variation in the pathogenesis of infectious diseases.
Kim
Sung-Kwon
SK
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Cornberg
Markus
M
Wang
Xiaoting Z
XZ
Chen
Hong D
HD
Selin
Liisa K
LK
Welsh
Raymond M
RM
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007156:Immunologic Memory; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000472:pathogenicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology* / Q000472:pathogenicity
D018984:Epitopes, T-Lymphocyte; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain