Selective CD4+ T Cell Help for Antibody Responses to a Large Viral Pathogen: Deterministic Linkage of Specificities
Open accessAbstract
Antibody responses are critical components of protective immune responses to many pathogens, but parameters determining which proteins are targeted remain unclear. Vaccination with individual MHC-II-restricted vaccinia virus (VACV, smallpox vaccine) epitopes revealed that CD4(+) T cell help to B cells was surprisingly nontransferable to other virion protein specificities. Many VACV CD4(+) T cell responses identified in an unbiased screen targeted antibody virion protein targets, consistent with deterministic linkage between specificities. We tested the deterministic linkage model by efficiently predicting new vaccinia MHC II epitopes (830% improved efficiency). Finally, we showed CD4(+) T cell help was limiting for neutralizing antibody development and protective immunity in vivo. In contrast to the standard model, these data indicate individual proteins are the unit of B cell-T cell recognition for a large virus. Therefore, MHC restriction is a key selective event for the antiviral antibody response and is probably important for vaccine development to large pathogens.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The magnitude of spike-specific CD4+ T cell responses correlated positively with S1-binding IgG and with the strength of spike-specific CD8+ T cell responses.
“The magnitude of S-specific CD4 + T cell responses correlated positively with S1-binding IgG (Extended Data Fig. 6a) and, consistent with the concept of intramolecular help 30 , also with the strength of S-specific CD8 + T cell responses (Extended Data Fig. 6b).”
From BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans (2021) · cites this paper as [30]
The citation lists haven’t been fetched yet
References 57 · Cited by 168
- Authors
- Sette, A., Moutaftsi, M., Moyron-Quiroz, J., McCausland, M. M., Davies, D. H., Johnston, R. J., Peters, B., Rafii-El-Idrissi Benhnia, M., Hoffmann, J., Su, H.-P., Singh, K., Garboczi, D. N., Head, S., Grey, H., Felgner, P. L., & Crotty, S.
- Affiliations
- La Jolla Institute for Immunology (US)
- University of California, Irvine (US)
- Scripps Research Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Crotty, Shane
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 28
- Issue
- 6
- Pages
- 847-858
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2504733
- OpenAlex
- W2151809231
- Cited by
- 168
- References
- 57
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 11 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 11 · 2013: 15 · 2012: 17
- FWCI
- 7.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1908 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health (266200400024)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- CD4+ T cell help, antibody response, vaccinia virus, MHC class II epitopes, neutralizing antibodies, protective immunity, vaccine development, epitope prediction
- MeSH terms
- Animals, Antibodies, Viral, Antibody Specificity, Epitopes, Histocompatibility Antigens Class II, Antigens, Viral, B-Lymphocytes, Mice, Inbred C57BL, Mice, Mutant Strains, Neutralization Tests, Smallpox Vaccine, Vaccinia, Vaccinia virus, CD4-Positive T-Lymphocytes, Adoptive Transfer, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
