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Cited by 312T-cell and B-cell ImmunologyImmunotherapy and Immune Responsesvaccines and immunoinformatics approaches

Cross-reactivities in memory cytotoxic T lymphocyte recognition of heterologous viruses.

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Selin, L K, Nahill, S R, Welsh, R M·1994·The Journal of experimental medicine
DOI 10.1084/jem.179.6.1933PMC PMC2191532
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Abstract

Analyses of the relationships between different viruses and viral proteins have focused on homologies between linear amino acid sequences, but cross-reactivities at the level of T cell recognition may not be dependent on a conserved linear sequence of several amino acids. The CTL response to Pichinde virus (PV) and vaccinia virus (VV) in C57BL/6 mice previously immunized with lymphocytic choriomeningitis virus (LCMV) included the reactivation of memory cytotoxic T lymphocyte (CTL) specific to LCMV. Limiting dilution assays (LDA) demonstrated that at least part of this reactivation of memory cells in LCMV-immune mice related to cross-reactivity at the clonal level, even though acute infections with these viruses in nonimmune mice elicited CTL responses that did not cross-react in conventional bulk CTL assays. Precursor CTL (pCTL) to LCMV were generated in splenic leukocytes from LCMV-immune mice acutely infected with PV or VV when stimulated in vitro with only the second virus but not with uninfected peritoneal exudate cells (PECs). Cytotoxicity mediated by LCMV-specific CTL clones activated by PV infection was greatly inhibited by anti-CD8 antibody, suggesting that these memory CTL clones recognizing LCMV-infected targets were of low affinity. LCMV-immune splenocytes stimulated in vitro with PV or VV demonstrated a low but significant precursor frequency (p/f) to the heterologous viruses, and splenocytes from PV- or VV-immune mice when stimulated in vitro against LCMV generated a low but significant p/f to LCMV. Short-term CTL clones cross-reactive between LCMV and PV were derived from splenic leukocytes from LCMV-immune mice acutely infected with PV. To distinguish whether the cross-reactivity was directed against a viral peptide or a virus-induced endogenous cellular neoantigen, we demonstrated that a pCTL frequency to PV about 1/4-1/7 that of the frequency to LCMV could be generated from LCMV-immune splenic leukocytes stimulated with the immunodominant LCMV NP peptide. A partially homologous PV peptide generated from the equivalent site to the LCMV NP peptide did not sensitize targets to lysis by either LCMV- or PV-specific CTLs, suggesting that the cross-reactivity in killing was not due to evolutionarily conserved equivalent sequences. Experiments also indicated that prior immunity to one virus could modulate future primary immune responses to a second virus. Elevated pCTL frequencies to PV were seen after acute PV infection of LCMV-immune mice, and elevated pCTL frequencies to LCMV were seen after acute LCMV infection of PV- and VV-immune mice.(ABSTRACT TRUNCATED AT 400 WORDS)

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Authors
Selin, L. K., Nahill, S. R., & Welsh, R. M.
Affiliations
University of Massachusetts Chan Medical School (US)
ORCID
Selin, L K
Venue
The Journal of experimental medicine
Publisher
Rockefeller University Press
Published
1994-06-01
Volume
179
Issue
6
Pages
1933-1943
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.179.6.1933
PMC
PMC2191532
OpenAlex
W1970205828
Cited by
312
References
38
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 10 · 2014: 4 · 2013: 12 · 2012: 5
FWCI
8.78
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (AI 17672, AI 07272, T32AI007272)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR035506, AR 35506)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
T cell cross-reactivity, Pichinde virus, vaccinia virus, lymphocytic choriomeningitis virus, CD8+ T cell responses, C57BL/6 mice
MeSH terms
Animals, Base Sequence, Cell Line, Transformed, Cross Reactions, Cytotoxicity, Immunologic, Immunologic Memory, Killer Cells, Natural, Lymphocyte Depletion, Lymphocytic choriomeningitis virus, Mice, Inbred C57BL, Molecular Sequence Data, Oligopeptides, T-Lymphocytes, Cytotoxic, Time Factors, Vaccinia virus, Viral Vaccines, CD8 Antigens, Pichinde virus, Mice

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