# Jonathan W. Yewdell
**Jonathan Wilson Yewdell** (Jonathan W. Yewdell) is an American physician-scientist in cellular immunology and virology who serves as Chief of the Cellular Biology Section of the Laboratory of Viral Diseases at the [National Institute of Allergy and Infectious Diseases](https://www.edgepedia.org/national-institute-of-allergy-and-infectious-diseases) (NIAID), a section established in 1993 on the NIH Main Campus in [Bethesda, Maryland](https://www.edgepedia.org/bethesda-maryland).[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) He is known for work on how peptides are generated for CD8+ T cell immunosurveillance, including the hypothesis that defective ribosomal products (DRiPs) are a significant source of self and viral peptides for [MHC class I](https://www.edgepedia.org/mhc-class-i) (cell-surface molecules displaying peptide fragments to immune T cells) molecules, and for studies of immunodominance and influenza immunity.[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) • [2](https://www.scilifelab.se/event/spotlight-seminar-jon-yewdell/) • [3](https://doi.org/10.4049/jimmunol.157.5.1823) His NIAID profile lists research areas spanning DRiP-derived MHC class I ligands, non-canonical protein translation, influenza, and coronavirus evolution and antigenic variation, B-cell immunodominance to influenza A virus, and identification of novel viral proteins.[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd)
| Key fact | Detail |
|---|---|
| Current role | Chief of the Cellular Biology Section of the Laboratory of Viral Diseases at NIAID[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) • [4](https://irp.nih.gov/pi/jonathan-yewdell) |
| Education | A.B. in biochemistry, Princeton, 1975; M.D. and Ph.D. in immunology, University of Pennsylvania, 1981[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) |
| Career path | Wistar Institute assistant professor 1983–1987; NIH Laboratory of Viral Diseases from 1987; section chief from 1993[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) |
| Signature work | 'The binary logic of antigen processing and presentation to T cells' (Cell, 1990) and the 1988 Science paper showing cells process exogenous proteins for CTL recognition[5](https://europepmc.org/article/MED/1695549) • [6](https://doi.org/10.1126/science.3257585); ["A novel influenza A virus mitochondrial protein that induces cell death"](https://doi.org/10.1038/nm1201-1306), *Nature Medicine*, 2001 |
| DRiPs hypothesis | Defective ribosomal products, produced entropically during protein synthesis, are a significant source of MHC class I peptides[3](https://doi.org/10.4049/jimmunol.157.5.1823) |
| Model systems | Influenza A, SARS-CoV-2, vaccinia, and other viruses[2](https://www.scilifelab.se/event/spotlight-seminar-jon-yewdell/) |
| Honor | Distinguished Fellow of the American Association of Immunologists, Class of 2026[7](https://www.aai.org/Awards/Career-Awards/Distinguished-Fellows-of-AAI/Current-Recipients) |
## Education and career
Yewdell received an A.B. in biochemistry magna cum laude from Princeton University in 1975, working with Arnold Levine on an undergraduate thesis concerning immune recognition of virus-transformed cells.[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) He then earned an M.D. and a Ph.D. in immunology from the University of Pennsylvania in 1981, working with Walter Gerhard on using monoclonal antibodies to understand influenza A virus hemagglutinin antigenicity and function.[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) As a postdoctoral fellow he worked with Sir David Lane at Imperial College in London, studying the p53 protein.[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd)
From 1983 to 1987 he was an assistant professor at the Wistar Institute in Philadelphia.[1](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd) He is listed by the NIH Intramural Research Program as a Senior Investigator in the Cellular Biology and Viral Immunology Section of NIAID's Division of Intramural Research.[4](https://irp.nih.gov/pi/jonathan-yewdell)
## Representative work
The 1988 Science paper on exogenous processing showed that cells exposed to intact, noninfectious influenza virus are recognized by class I-restricted anti-influenza cytotoxic T lymphocytes, with both internal and external virion proteins processed for recognition.[6](https://doi.org/10.1126/science.3257585) [Sensitization](https://www.edgepedia.org/sensitization) required inactivation of viral neuraminidase activity and could be blocked by preventing fusion of viral and cellular membranes, suggesting processing depends on introduction of exogenous proteins into the cytoplasm.[6](https://doi.org/10.1126/science.3257585) In a 2024 interview, Yewdell recalled that his early hypothesis that T cells recognized native proteins on the infected cell surface was shown wrong, and that the experiments clearly showed that T cells recognize short peptides from viral proteins.[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC11460944/)
The 1990 Cell article, 'The binary logic of antigen processing and presentation to T cells,' appeared in that journal in 1990 and is indexed under Yewdell's ORCID 0000-0002-3826-1906.[5](https://europepmc.org/article/MED/1695549) The processing theme continued in his 1992 Advances in [Immunology](https://www.edgepedia.org/immunology) review 'Cell Biology of Antigen Processing and Presentation to MHC Class I Molecule-Restricted T Lymphocytes,'[10](https://doi.org/10.1016/s0065-2776(08)60875-5) and a 1993 Journal of Experimental Medicine article from the Laboratory of Viral Diseases reported that presentation of numerous viral peptides to MHC class I-restricted T lymphocytes is mediated by the human MHC-encoded transporter (TAP) or by a hybrid mouse-human transporter.[11](https://rupress.org/jem/article/177/6/1785/50439/Presentation-of-numerous-viral-peptides-to-mouse)
## DRiPs and immunodominance
In a September 1996 Journal of Immunology paper, Yewdell proposed that a significant source of self and viral peptides are defective ribosomal products (DRiPs): prematurely terminated polypeptides and misfolded polypeptides produced from translation of bona fide mRNAs in the proper reading frame.[3](https://doi.org/10.4049/jimmunol.157.5.1823) The paper argued that DRiPs are produced entropically, from the inevitable imperfections inherent to protein synthesis or folding, and that DRiP formation may be enhanced by infection-induced changes in cellular physiology or inflammatory cytokines.[3](https://doi.org/10.4049/jimmunol.157.5.1823) A later review consolidated the idea, defining DRiPs as a subset of rapidly degraded polypeptides that provide peptide ligands for MHC class I molecules and stating that findings on DRiP biogenesis place DRiPs at the center of the MHC class I antigen-processing field.[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC3200450/) The current model holds that many cellular peptides, and likely nearly all viral peptides, derive from rapidly degraded proteins consisting of DRiPs and short-lived proteins (SLiPs).[2](https://www.scilifelab.se/event/spotlight-seminar-jon-yewdell/)
His lab has also shaped the study of immunodominance, the unequal T-cell response to different determinants of one antigen. The 1999 Annual Review of Immunology article on immunodominance in MHC class I-restricted T lymphocyte responses reviews the molecular and cellular basis of the phenomenon, and quantifies the bottlenecks: only about 1/200 of potential peptide determinants bind a given class I allele above the immunogenicity threshold, and the immunogenicity of subdominant determinants is often limited by immunodomination, suppression mediated by CD8+ T cells specific for immunodominant determinants.[13](https://www.annualreviews.org/content/journals/10.1146/annurev.immunol.17.1.51) After moving to NIH, the lab's findings have included the DRiP origin of viral peptides, intravital imaging of antiviral immunity, and the discovery of new influenza virus gene products.[8](https://www.metascience2019.org/invited-speakers/jonathan-yewdell/)
## Laboratory and methods
The stated mission of the Yewdell lab is to extend a basic understanding of the interaction between the host and viruses, and to use viruses as tools to better understand cell biology.[14](https://www.niaid.nih.gov/research/yewdell-research-group) The lab uses influenza A, SARS-CoV-2, vaccinia, and other viruses to explore basic elements of cell biology, virology, and immunology.[2](https://www.scilifelab.se/event/spotlight-seminar-jon-yewdell/)
## Recent work
A 2024 Science Immunology paper reported that C1q enables influenza hemagglutinin stem-binding antibodies to block viral attachment and broadens the antibody escape repertoire.[4](https://irp.nih.gov/pi/jonathan-yewdell) In a May 2023 talk at Westlake University, Yewdell reported that complement protein C1q enhances the antiviral activity of influenza HA head-specific antibodies and helps stem-specific antibodies inhibit attachment and membrane fusion across multiple influenza subtypes, and that mutations at the K322 site of a stem-specific antibody, which interacts with C1q, abolish these effects.[15](https://en.westlake.edu.cn/news_events/westlakenews/UniversityNews/202305/t20230505_35909.html) In January 2026 he visited the International Research Center for Infectious Diseases (IVReD) at Hokkaido University, where future collaborative research was discussed; the announcement describes his work as internationally recognized for elucidating mechanisms of antigen presentation via MHC class I molecules and for advancing understanding of host immune responses to influenza viruses.[16](https://www.ivred.hokudai.ac.jp/en/news/7909)
## Honors and recognition
The American Association of Immunologists named Yewdell a Distinguished Fellow of AAI in the Class of 2026, a program that annually recognizes members for distinguished careers and outstanding scientific contributions as well as service to AAI and the immunology community; he has been an AAI member since 2001.[7](https://www.aai.org/Awards/Career-Awards/Distinguished-Fellows-of-AAI/Current-Recipients)
## References
1. [Jonathan Wilson Yewdell, M.D., Ph.D. | NIAID](https://www.niaid.nih.gov/research/jonathan-wilson-yewdell-md-phd)
2. [Drips and SliPS and Retirees, Oh My!, SciLifeLab](https://www.scilifelab.se/event/spotlight-seminar-jon-yewdell/)
3. [Defective ribosomal products (DRiPs) (Journal of Immunology, 1996)](https://doi.org/10.4049/jimmunol.157.5.1823)
4. [Jonathan Wilson Yewdell, M.D., Ph.D. | NIH Intramural Research Program](https://irp.nih.gov/pi/jonathan-yewdell)
5. [The binary logic of antigen processing and presentation to T cells (Cell, 1990)](https://europepmc.org/article/MED/1695549)
6. [Cells Process Exogenous Proteins for Recognition by Cytotoxic T Lymphocytes (Science, 1988)](https://doi.org/10.1126/science.3257585)
7. [Distinguished Fellows of AAI, Class of 2026](https://www.aai.org/Awards/Career-Awards/Distinguished-Fellows-of-AAI/Current-Recipients)
8. [Jonathan Yewdell, Metascience 2019 Symposium](https://www.metascience2019.org/invited-speakers/jonathan-yewdell/)
9. [Jonathan Yewdell Discusses Viral Immunology (Pathogens and Immunity, 2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11460944/)
10. https://doi.org/10.1016/s0065-2776(08)60875-5
11. [Presentation of numerous viral peptides ... mediated by the human MHC-encoded transporter (JEM, 1993)](https://rupress.org/jem/article/177/6/1785/50439/Presentation-of-numerous-viral-peptides-to-mouse)
12. [DRiPs Solidify: Progress in Understanding Endogenous MHC Class I Antigen Processing](https://pmc.ncbi.nlm.nih.gov/articles/PMC3200450/)
13. [Immunodominance in MHC Class I–Restricted T Lymphocyte Responses (Annual Review of Immunology, 1999)](https://www.annualreviews.org/content/journals/10.1146/annurev.immunol.17.1.51)
14. [Yewdell Research Group, NIAID](https://www.niaid.nih.gov/research/yewdell-research-group)
15. [New Insights into Host-Virus Interactions, Westlake University](https://en.westlake.edu.cn/news_events/westlakenews/UniversityNews/202305/t20230505_35909.html)
16. [Visit: NIH/NIAID Dr. Jonathan Wilson Yewdell, IVReD, Hokkaido University](https://www.ivred.hokudai.ac.jp/en/news/7909)
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*Topic: Encyclopedia › Life and health › Life and health scientists › Medical and health researchers › Immunology and allergy researchers › Infection and vaccine immunity researchers*
*Initially written Sep 20, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026; Oct 15, 2026 · Last review: Sep 25, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license