Private specificities of CD8 T cell responses control patterns of heterologous immunity
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Program in Immunology and Virology; Department of Pathology
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Exp Med. 2005 Feb 21;201(4):523-33. Epub 2005 Feb 14. Link to article on publisher's site
The Journal of experimental medicine
Kim, Sung-Kwon; Cornberg, Markus; Wang, Xiaoting Z.; Chen, Hong D.; Selin, Liisa K.; and Welsh, Raymond M., "Private specificities of CD8 T cell responses control patterns of heterologous immunity" (2005). GSBS Student Publications. 603.