# Wayne M. Yokoyama
Wayne M. Yokoyama is an American physician-scientist and immunologist at Washington University School of Medicine in St. Louis, where he is the Sam and Audrey Loew Levin Professor of Medicine and a Professor of Pathology and [Immunology](https://www.edgepedia.org/immunology).[1](https://profiles.wustl.edu/en/persons/wayne-yokoyama/) His laboratory studies the basic mechanisms of innate immunity and the immune response to viruses, with a particular interest in the receptors expressed by natural killer (NK) cells, their ligands, and viral immune evasion.[1](https://profiles.wustl.edu/en/persons/wayne-yokoyama/) He is known for establishing the molecular basis of NK cell target recognition: his group discovered that NK cells carry inhibitory receptors for major histocompatibility complex (MHC) class I molecules that dictate NK cell specificity, a finding the American Academy of Arts and Sciences credits with creating a paradigm shift in the understanding of cell recognition.[2](https://www.amacad.org/person/wayne-m-yokoyama) His clinical background is in rheumatology, especially the etiology and pathogenesis of rheumatoid arthritis.[1](https://profiles.wustl.edu/en/persons/wayne-yokoyama/)
| Key facts | |
| --- | --- |
| Field | Immunology; natural killer cell receptors, self-tolerance, and innate antiviral immunity[1](https://profiles.wustl.edu/en/persons/wayne-yokoyama/) |
| Position | Sam and Audrey Loew Levin Professor of Medicine; Professor of Pathology and Immunology; Director, Medical Scientist Training Program; Associate Dean, Division of Physician-Scientists, Washington University[1](https://profiles.wustl.edu/en/persons/wayne-yokoyama/) • [3](https://physicianscientists.wustl.edu/people/wayne-yokoyama/) |
| Training | B.A. in biology, University of Rochester; M.D., University of Hawaii (1974–1978); internal medicine and rheumatology training, University of Iowa Hospitals; postdoctoral training in basic immunology, NIH[4](https://source.washu.edu/2007/07/yokoyama-named-director-of-medical-scientist-training-program/) • [5](https://orcid.org/0000-0002-0566-7264) • [6](https://medicine.washu.edu/news/about/faculty-recognition/distinguished-faculty-awards/dfa-2016/wayne-m-yokoyama-md/) |
| Career | UCSF assistant professor; Mount Sinai associate professor, 1992; HHMI associate investigator, 1994; chief of Rheumatology, WashU, 1995–2007; HHMI Investigator, 1997–2017; MSTP director, 2007[4](https://source.washu.edu/2007/07/yokoyama-named-director-of-medical-scientist-training-program/) • [7](https://www.hhmi.org/scientists/wayne-m-yokoyama) |
| Signature work | "Licensing of natural killer cells by host major histocompatibility complex class I molecules," Nature 436:709–713 (2005)[8](https://europepmc.org/article/med/16079848) |
| Honors | National Academy of Sciences (2007); American Academy of Arts and Sciences (2009); National Academy of Medicine (2012); AAI President, 2017–18[9](https://www.nasonline.org/directory-entry/wayne-m-yokoyama-noz3ss/) • [10](https://www.aai.org/About/History/Past-Presidents-and-Officers/Wayne-M-Yokoyama,-M-D) |
| Current lab focus | NK cell receptors in viral infection and tumors, tolerance to self, herpesviruses, uveitis, and neuro-sarcoidosis[11](https://rheumatology.wustl.edu/research-2/research/yokoyama-lab/) |
## Training and career
A native of Maui, Hawaii, Yokoyama earned an undergraduate degree in biology from the [University of Rochester](https://www.edgepedia.org/university-of-rochester) and the M.D. from the University of Hawaii John A. Burns School of Medicine, where he was enrolled from September 1974 to May 1978.[4](https://source.washu.edu/2007/07/yokoyama-named-director-of-medical-scientist-training-program/) • [5](https://orcid.org/0000-0002-0566-7264) He completed an internal medicine residency and a rheumatology and immunology clinical fellowship at the University of Iowa Hospitals, and received postdoctoral training in basic immunology at the National Institutes of Health, where he was also a research fellow.[6](https://medicine.washu.edu/news/about/faculty-recognition/distinguished-faculty-awards/dfa-2016/wayne-m-yokoyama-md/) • [4](https://source.washu.edu/2007/07/yokoyama-named-director-of-medical-scientist-training-program/)
His academic career began as an assistant professor of medicine at the [University of California, San Francisco](https://www.edgepedia.org/university-of-california-san-francisco). In 1992 he moved to Mount Sinai School of Medicine as an associate professor of medicine and of microbiology, and in 1994 he became an associate investigator of the [Howard Hughes Medical Institute](https://www.edgepedia.org/howard-hughes-medical-institute).[4](https://source.washu.edu/2007/07/yokoyama-named-director-of-medical-scientist-training-program/) In 1995 Washington University recruited him as chief of the Rheumatology Division, a position he held until 2007, when he became director of the Medical Scientist Training Program (MSTP).[6](https://medicine.washu.edu/news/about/faculty-recognition/distinguished-faculty-awards/dfa-2016/wayne-m-yokoyama-md/) He served as an HHMI Investigator from 1997 to 2017 and is now an HHMI Investigator Emeritus.[7](https://www.hhmi.org/scientists/wayne-m-yokoyama) He currently directs the MSTP and serves as Associate Dean of WashU Medicine's Division of Physician-Scientists.[3](https://physicianscientists.wustl.edu/people/wayne-yokoyama/) In the MSTP role he meets individually with every student and has mentored nearly 500.[6](https://medicine.washu.edu/news/about/faculty-recognition/distinguished-faculty-awards/dfa-2016/wayne-m-yokoyama-md/)
## Natural killer cells, Ly49 and missing-self recognition
NK cells are lymphocytes that destroy tumor and virus-infected cells, and their receptors are germline-encoded by a complex of clustered genes, unlike the receptors of closely related T cells, which arise by gene rearrangement.[2](https://www.amacad.org/person/wayne-m-yokoyama) • [9](https://www.nasonline.org/directory-entry/wayne-m-yokoyama-noz3ss/) Ironically, the first NK cell receptors identified were inhibitory: they damp NK cell activation and specifically recognize [MHC class I](https://www.edgepedia.org/mhc-class-i) molecules, the same self-markers T cells use to identify invaders.[9](https://www.nasonline.org/directory-entry/wayne-m-yokoyama-noz3ss/)
The mouse receptor family at the center of this work is Ly49. When an NK cell binds MHC class I through such a receptor, the cell is shut off; only when the self signal is insufficient is it released to act, a mechanism that explains "missing-self" recognition and counters viruses that depress MHC class I to evade T cells.[12](https://source.washu.edu/2011/10/rheumatologist-cracks-molecular-mystery/) Licensing and effector inhibition by Ly49 receptors involve the same recognition site on MHC class I ligands, and the intact ITIM cytoplasmic motif of the inhibitory receptor is required for licensing.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC3151350/) The human parallel receptors, KIRs specific for self-HLA, show the same pattern of more robust cytokine production, indicating that the mouse Ly49 and human KIR systems are related by convergent evolution.[13](https://pmc.ncbi.nlm.nih.gov/articles/PMC3151350/)
## Representative work
The 2005 Nature paper "Licensing of natural killer cells by host major histocompatibility complex class I molecules" (Nature 436:709–713, 1 August 2005) demonstrated that NK cells acquire functional competence through "licensing" by self-MHC molecules, a positive role for MHC-specific inhibitory receptors that requires the cytoplasmic inhibitory motif and produces two types of self-tolerant NK cells, licensed and unlicensed.[8](https://europepmc.org/article/med/16079848) According to Yokoyama's 2006 review in *Immunological Reviews*, which consolidated the model, licensed cells have effector responses inhibited by self-MHC class I through the same receptors that conferred licensing, while unlicensed cells are functionally incompetent.[15](https://doi.org/10.1111/j.1600-065x.2006.00458.x)
## Honors, funding and leadership
Yokoyama was elected to the National Academy of Sciences in 2007 (primary section Immunology and [Inflammation](https://www.edgepedia.org/inflammation)),[9](https://www.nasonline.org/directory-entry/wayne-m-yokoyama-noz3ss/) became an AAAS Fellow and a member of the American Academy of Arts and Sciences in 2009, received the Lee C. Howley Sr. Prize for Research in [Arthritis](https://www.edgepedia.org/arthritis) from the National Arthritis Foundation in 2010, and was elected to the [National Academy of Medicine](https://www.edgepedia.org/national-academy-of-medicine) in 2012.[10](https://www.aai.org/About/History/Past-Presidents-and-Officers/Wayne-M-Yokoyama,-M-D) He received the Novartis Prize for Basic Research in Immunology; the American Association of Immunologists dates it to 2001, while his own alumni interview gives 2002.[10](https://www.aai.org/About/History/Past-Presidents-and-Officers/Wayne-M-Yokoyama,-M-D) • [16](https://alumni.medicine.uiowa.edu/news/2017/05/qa-wayne-m-yokoyama-md) He was elected to the American Society for Clinical Investigation, the Association of American Physicians, and the American Academy of Microbiology.[16](https://alumni.medicine.uiowa.edu/news/2017/05/qa-wayne-m-yokoyama-md) Within AAI, which he joined in 1984, he was a Council member from 2012 to 2020, President from 2017 to 2018, and a Distinguished Fellow in 2020.[10](https://www.aai.org/About/History/Past-Presidents-and-Officers/Wayne-M-Yokoyama,-M-D) At WashU he received the 2011 Carl and Gerty Cori Faculty Achievement Award and the Samuel R. Goldstein Leadership Award in Medical Student Education.[6](https://medicine.washu.edu/news/about/faculty-recognition/distinguished-faculty-awards/dfa-2016/wayne-m-yokoyama-md/) His NIH support has included R01 AI033903, R01 AI051345, R37 AI034385 for the licensing work[8](https://europepmc.org/article/med/16079848) and R01 AI129545, "Natural Killer Cell Tolerance to Self," which ran from March 2017 to February 2022 under NIAID.[17](https://grantome.com/grant/NIH/R01-AI129545-05)
## References
1. [Wayne Yokoyama – WashU Research Profiles](https://profiles.wustl.edu/en/persons/wayne-yokoyama/)
2. [Wayne M. Yokoyama | American Academy of Arts and Sciences](https://www.amacad.org/person/wayne-m-yokoyama)
3. [Wayne Yokoyama | Physician-Scientists | Washington University in St. Louis](https://physicianscientists.wustl.edu/people/wayne-yokoyama/)
4. [Yokoyama named director of Medical Scientist Training Program – The Source – WashU](https://source.washu.edu/2007/07/yokoyama-named-director-of-medical-scientist-training-program/)
5. [ORCID record for Wayne M. Yokoyama](https://orcid.org/0000-0002-0566-7264)
6. [Wayne M. Yokoyama, MD – WashU Medicine Distinguished Faculty Awards 2016](https://medicine.washu.edu/news/about/faculty-recognition/distinguished-faculty-awards/dfa-2016/wayne-m-yokoyama-md/)
7. [Wayne M. Yokoyama, MD | Investigator Emeriti | 1997-2017 – HHMI](https://www.hhmi.org/scientists/wayne-m-yokoyama)
8. [Licensing of natural killer cells by host major histocompatibility complex class I molecules (Nature, 2005) – Europe PMC](https://europepmc.org/article/med/16079848)
9. [Wayne M. Yokoyama – National Academy of Sciences member directory](https://www.nasonline.org/directory-entry/wayne-m-yokoyama-noz3ss/)
10. [Wayne M. Yokoyama, M.D. – The American Association of Immunologists](https://www.aai.org/About/History/Past-Presidents-and-Officers/Wayne-M-Yokoyama,-M-D)
11. [Yokoyama Lab – Division of Rheumatology – WashU](https://rheumatology.wustl.edu/research-2/research/yokoyama-lab/)
12. [Rheumatologist Cracks Molecular Mystery – The Source – WashU](https://source.washu.edu/2011/10/rheumatologist-cracks-molecular-mystery/)
13. [Unifying concepts of MHC-dependent natural killer cell education – PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3151350/)
14. [Natural Killer Cells: Tolerance to Self and Innate Immunity to Viral Infection and Malignancy – PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3900292/)
15. [Licensing of natural killer cells by self-major histocompatibility complex class I (Immunological Reviews, 2006)](https://doi.org/10.1111/j.1600-065x.2006.00458.x)
16. [Q&A with Wayne M. Yokoyama, MD | University of Iowa Carver College of Medicine](https://alumni.medicine.uiowa.edu/news/2017/05/qa-wayne-m-yokoyama-md)
17. [Natural Killer Cell Tolerance to Self – NIH R01 AI129545 (grantome)](https://grantome.com/grant/NIH/R01-AI129545-05)
18. [Expression of a single inhibitory Ly49 receptor is sufficient to license NK cells (bioRxiv, 2024)](https://www.biorxiv.org/content/10.1101/2024.06.04.597367v1)
---
*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in immunology, microbiology, and virology › NK cells and innate lymphocytes*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026 · Last review: Sep 25, 2026*
*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*
License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license