Prof. Dr. Jim Kaufman
Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, UK, and Visiting Researcher of the Department of Pathology, University of Cambridge, UK

This is a Science Portrait of Prof. Dr. Jim (James Frederick) Kaufman, Institute of Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, UK, and Visiting Researcher of the Department of Pathology, University of Cambridge, UK. He will give a presentation at Fujita Health University, by Zoom, on Friday, October 29.

Prof. Kaufman is one of the world leaders in the science of major histocompatibility complex (MHC) molecules, and his specialty is their evolution. MHC molecules are critical to the adaptive immune system by presenting peptides to T lymphocytes. MHC molecules are fascinating because they show more variation between individuals than any other human molecules. Until he retired there last year, Prof. Kaufman was professor at Cambridge University, UK. He is particularly famous for his well-supported models that in evolution MHC class II came before MHC class I, and that MHC allelic polymorphism importantly concerns differences in expression levels and narrow versus broad repertoires of presented peptides (“specialists” versus “generalists”). He has a beautiful style of writing and has written many articles in top-tier review journals. This sense for explaining will serve us well when he will tell us about “The MHC and disease: a new understanding of how it works,” in which he will discuss MHC molecules and their evolution in general (he knows that we are not an audience of specialists) and his generalists/specialists model in particular.  

Prof. Kaufman studied Chemistry at the University of Washington, graduating magna cum laude. After this, he did his Ph.D. studies at Harvard University in the group of Jack L. Strominger, winner of, e.g., the Lasker Award and the Japan Prize. In that group, the young Jim was important in the first biochemical, genetic, and theoretical analyses of major histocompatibility complex (MHC) class I and II molecules (e.g., Kaufman and Strominger, Nature 1982; Kaufman et al. Cell 1984; the 1984 paper was the first in which he proposed that—in evolution—MHC class II came before MHC class I). It was also Jim who suggested his friend, Pamela Björkman who did her Ph.D. studies in the same group, to be the first to elucidate the structure of MHC molecules. This she did for HLA-A2 with help of the Don Wiley group (Bjorkman et al., Nature 1987); for a sequence of events, in which Jim is mentioned, see memories by Jack Strominger. Based on this elucidation of the HLA-A2 structure, even very recently, Björkman and Strominger were mentioned as potential candidates for a Nobel Prize.

After Harvard, Jim became an independent member scientist at the Basel Institute for Immunology. This was a famous institute (1971-2000) where the company Hoffmann-La Roche permanently allowed around 50, mostly young, scientists to do basic immunology research in freedom. Several of those scientists would eventually receive a Nobel Prize for their work (partially) done or optimized in Basel, including Niels K. Jerne and Georges J.F. Köhler (together with César Milstein of Cambridge University) in 1984 for theories on the adaptive immune system and the establishing of a method for the production of monoclonal antibodies, respectively, and Susumu Tonegawa (who left the institute in the year Jim arrived) in 1987 for his discovery of the genetic principle for generation of antibody diversity. Jim used his Basel period (1981-1995) as a start to establish himself as a leader in the field of chicken MHC and the evolution of MHC, something which he is still to date. Reasons for Jim to dedicate much of his MHC research to chicken are that their genomic organization of (classical) MHC genes is relatively simple compared to most mammals (Kaufman et al., Nature 1999) and that their allelic MHC variation is linked with pronounced differences in disease resistance (Kaufman, Philos Trans R Soc Lond B Biol Sci 2000; Halabi et al., Plos Biology 2021). In humans, MHC molecules show the highest polymorphism (allelic variation between individuals) of all molecules, but the reasons for this polymorphism are (arguably) still not well understood (e.g., Yamaguchi and Dijkstra, Cells 2019; Radwan et al., Trends in Genetics 2020). Working in a simpler model like chicken may increase the chance of finally becoming sure about the reasons of MHC polymorphism, which is a holy grail for many MHC researchers.

After Basel, in 1995, Jim became first Deputy Head and then Head (2002) of the Division of Immunology and Pathogenesis, Institute for Animal Health, Compton and Pirbright, UK. In this function, he had an important task in trying to help the poultry industry. This was followed, in 2007, by becoming a Professor of Comparative Immunogenetics at the University of Cambridge, UK, where he retired in 2020 to become Professor of Immunology at the University of Edinburgh, UK. In all these years in the UK, Prof. Kaufman did a lot of the necessary groundwork for chicken MHC, such as the genetic analysis of allelic polymorphisms and haplotypes, structural elucidation of chicken MHC molecules, sequencing of the peptides that these molecules bind, and analyzing disease associations. Despite being relatively straightforward, Prof. Kaufman’s dedication to precision and sharp eye for the scientifically new, allowed this research to be published in top journals (e.g., Koch et al., Immunity 2007). Gradually, all this serious groundwork accumulated into an entirely new concept of MHC polymorphism, distinguishing between “specialists” and “generalists” that have a narrow or broad repertoire of presented peptides (Kaufman, Trends in Immunology 2018). Quite recently, this concept has been supported by findings in humans.

I have been studying MHC evolution from 1997, mostly from the perspective of fish. Throughout all those years, Prof. Kaufman’s work has been a beacon of quality and research integrity. It was also always easy to tell when one of my papers had been reviewed by Prof. Kaufman, because of the beautiful English, the depth and detail of the comments, and the supportive nature (although he can be brusque about mistakes). I will never forget that when I was applying for a job, he took the time and effort to write a long and careful letter on my behalf. So, it is with very great honor and pleasure that I can introduce Prof. Kaufman as a speaker at Fujita Health University.

 

What Prof. Kaufman likes about Science

I asked Prof. Kaufman to also write some personal words for this blog. For that, he wrote:

What I like about science: “Every day is a fun adventure, as I learn new things from our research and from my colleagues, and suddenly realise connections that had never occurred to me.”

 

                                                                  CURRICULUM VITAE

 

BIRTH:                             October 6, 1952, in New York City

 

EDUCATION:

1970-1974                      University of Washington, BSc (magna cum laude) in Chemistry

Thesis with Professor Martin Gouterman:

Synthesis and Spectroscopic Characterization of Uranyl Porphyrins.

1974-1983                      Harvard University, Ph.D. in Biochemistry and Molecular Biology:

Thesis with Professor Jack Strominger:

Proteolytic Dissection of MHC Class II Antigen Structure

 

PROFESSIONAL EXPERIENCE:

1981-1995                     Independent Member Scientist, Basel Institute for Immunology,

Basel, Switzerland

1995-2007                     Deputy Head and then (2002) Head, Division of Immunology and

Pathogenesis, Institute for Animal Health, Compton and Pirbright, UK

2007-2019                     Professor of Comparative Immunogenetics, Division of Immunology,

Department of Pathology, University of Cambridge, Cambridge, UK

2016-2017                      Head, Division of Immunology, Department of Pathology, University of

Cambridge, Cambridge, UK

2020-present                 Professor of Immunology, Institute for Immunology and Infection

Research, University of Edinburgh, Edinburgh, UK

 

KEY HONOURS AND AWARDS:

1972                                 NORCUS Fellow, University of Washington

1990                                 Elected member of European Network of Immunology Institutes    

2012                                 Elected Fellow of Royal Society of Biology

2014                                 Elected member of the Medical Research Club (London)

2018                                 Elected member of the European Molecular Biology Organisation

(EMBO)

 

OTHERS:

Regarding memberships, committee tasks, teaching history, reviewing tasks, editorships, and rewarded grants, Prof. Kaufman has an impressive list matching his other achievements. Of these, I just like to summarize that he has been reviewer for >50 journals including Nature, Nature Communications, Nature Immunology, PNAS, and Science.

 

PUBLICATIONS

Prof. Kaufman has 172 publications, including in top-journals such as Nature (4x), Cell (2x), Nature Immunology (1x), Nucleic Acids Research (1x), Journal of Experimental Medicine (3x), EMBO Journal (1x), and PNAS (10x). Besides these papers, Prof. Kaufman regularly published in the top-tier review journals in the field of immunology. The below list is a combination of the papers that he selected in relation to his seminar, and papers that I selected for his Science Portrait. For a more complete list of his publications see his ORCID page. At the beginning of his career, Prof. Kaufman used the initials J.F., which for unity were changed in this list to only J.

1. Tregaskes CA, Kaufman J (2021) Chickens as a simple system for scientific discovery: The example of the MHC. Mol Immunol 135: 12-20.

2. Halabi S, Ghosh M, Stevanović S, Rammensee HG, Bertzbach LD, Kaufer BB, Moncrieffe MC, Kaspers B, Härtle S, Kaufman J (2021) The dominantly expressed class II molecule from a resistant MHC haplotype presents only a few Marek’s disease virus peptides by using an unprecedented binding motif. PLoS Biol 19:e3001057.

3. Tsakou-Ngouafo L, Paganini J, Kaufman J, Pontarotti P (2020) Origins of the RAG Transposome and the MHC.Trends Immunol 41(7): 561-571.

4. Kaufman J (2018) Unfinished business: evolution of the adaptive immune system of jawed vertebrates. Annu Rev Immunol 36: 383-409.

5. Kaufman J (2018) Generalists and specialists: a new view of how MHC class I molecules fight infectious pathogens. Trends Immunol 39: 367-379 (cover article).

6. Parker A, Kaufman J (2017) What chickens might tell us about the MHC class II system. Curr Opin Immunol 46: 23-29.

7. Tregaskes CA, Harrison M, Sowa AK, van Hateren A, Hunt LG, Vainio O, Kaufman J (2016) Surface expression, peptide repertoire and thermostability of chicken class I molecules correlate with peptide transporter specificity. Proc Natl Aca. Sci USA 113: 692-697.

8. Maccari G, Robinson J, Ballingall K, Guethlein LA, Grimholt U, Kaufman J, Ho CS, de Groot NG, Flicek P, Bontrop RE, Hammond JA, Marsh SG (2017) IPD-MHC 2.0: an improved inter-species database for the study of the major histocompatibility complex. Nucleic Acids Res 45(D1): D860-D864.

9. Kaufman J (2015) Co-evolution with chicken class I genes. Immunol Rev 267(1): 56-71.

10. Chappell P, Meziane EK, Harrison M, Magiera Ł, Hermann C, Mears L, Wrobel AG, Durant C, Nielsen LL, Buus S, Ternette N, Mwangi W, Butter C, Nair V, Ahyee T, Duggleby R, Madrigal A, Roversi P, Lea SM, Kaufman J (2015) Expression Levels of MHC Class I molecules are Inversely Correlated with Promiscuity of Peptide Binding. eLIFE 4: e05345.

11. Kaufman J (2015) What chickens would tell you about the evolution of antigen processing and presentation. Curr Opin Immunol 34C: 35-42.

12. Kaufman J (2015) Co-evolution with chicken class I genes. Immunol Rev 267: 56-71.

13. Kaufman J (2013) The Avian MHC (Chapter 8, pp 149-167). In: Avian Immunology, second edition; KA Schat, P Kaiser, B Kaspers, editors. Elsevier, Ltd.

14. Siddle HV, Kreiss A, Tovar C, Yuen CK, Cheng Y, Belov K, Swift K, Pearse AM, Hamede R, Jones ME, Skjødt K, Woods GM, Kaufman J (2013) Reversible epigenetic down-regulation of MHC molecules by devil facial tumour disease illustrates immune escape by a contagious cancer. Proc Natl Acad Sci U S A 110(13): 5103-8.

15. Walker BA, Hunt LG, Sowa AK, Skjødt K, Göbel TW, Lehner PJ, Kaufman J (2011) The dominantly-expressed class I molecule of the chicken MHC is explained by co-evolution with the polymorphic peptide transporter (TAP) genes. Proc Natl Acad Sci USA 108: 8396-8401.

16. Rogers SL, Viertlboeck BC, Göbel TW, Kaufman J (2008) Avian NK activities, cells and receptors. Semin Immunol 20(6): 353-60.

17. Koch M, Camp S, Collen T, Avila D, Salomonsen J, Wallny H-J, van Hateren A, Hunt LG, Jacob JP, Johnston F, Marston DA, Shaw I, Dunbar PR, Cerundolo VE, Jones EY, Kaufman J (2007) Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding. Immunity 27: 885-899.

18. Shaw I, Powell TA, Marston DA, Baker K, van Hateren A, Riegert P, Wiles MV, Milne S, Beck S, Kaufman J (2007) Different evolutionary histories of the two classical class I gene BF1 and BF2 illustrate drift and selection within stable MHC haplotypes of chickens. J Immunol 178: 5744-5752.

19. Wallny H-J, Avila D, Hunt LG, Powell TJ, Riegert P, Salomonsen J, Skjødt K, Vainio O, Vilbois F, Wiles MV, Kaufman J (2006) Peptide motifs of the single dominantly-expressed class I molecule can explain the striking MHC-determined response to Rous sarcoma virus in chickens. Proc Natl Acad Sci USA 103: 1434-1439.

20. Salomonsen J, Sørensen MR, Marston DA, Rogers SL, Collen T, van Hateren A, Smith AL, Beal RK, Skjødt K, Kaufman J (2005) Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc Natl Acad Sci U S A 102(24): 8668-73.

21. Wong et al. (International Chicken Polymorphism Map Consortium) (2004) A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. Nature 432(7018): 717-22.

22. Kaufman J (2002) The origins of the adaptive immune system: whatever next? Nat Immunol 3(12):1124-5.

23. Kaufman J, Milne S, Goebel TW, Walker BA, Jacob JP, Auffray C, Zoorob R, Beck S (1999) The chicken B locus is a minimal essential major histocompatibility complex. Nature 401: 923-925.

24. Kaufman J, Jacob J, Shaw I, Walker B, Milne S, Beck S, Salomonsen J (1999) Gene organisation determines evolution of function in the chicken MHC. Immunol Rev 167: 101-17.

25. Riegert P, Andersen R, Bumstead N, Döhring C, Dominguez-Steglich M, Engberg J, Salomonsen J, Schmid M, Schwager J, Skjødt K, Kaufman J (1996) The chicken beta 2-microglobulin gene is located on a non-major histocompatibility complex microchromosome: a small, G+C-rich gene with X and Y boxes in the promoter. Proc Natl Acad Sci U S A 93(3): 1243-8.

26. Kaufman J, Völk H, Wallny HJ (1995) A “minimal essential Mhc” and an “unrecognized Mhc”: two extremes in selection for polymorphism. Immunol Rev 143: 63-88.

27. Kaufman J, Salomonsen J, Flajnik M (1994) Evolutionary conservation of MHC class I and class II molecules–different yet the same. Semin Immunol 6(6): 411-24.

28. Kronenberg M, Brines R, Kaufman J (1994) MHC evolution: a long term investment in defense. Immunol Today 15(1): 4-6.

29. Kaufman J, Salomonsen J (1992) B-G: we know what it is, but what does it do? Immunol Today 13(1): 1-3.

30. Cosgrove D, Gray D, Dierich A, Kaufman J, Lemeur M, Benoist C, Mathis D (1991) Mice lacking MHC class II molecules. Cell 66(5): 1051-66.

31. Salomonsen J, Dunon D, Skjødt K, Thorpe D, Vainio O, Kaufman J (1991) Chicken major histocompatibility complex-encoded B-G antigens are found on many cell types that are important for the immune system. Proc Natl Acad Sci U S A 88(4): 1359-63.

32. Kishi H, Borgulya P, Scott B, Karjalainen K, Traunecker A, Kaufman J, von Boehmer H (1991) Surface expression of the beta T cell receptor (TCR) chain in the absence of other TCR or CD3 proteins on immature T cells. EMBO J 10(1): 93-100.

33. Kaufman J, Salomonsen J, Skjødt K, Thorpe D (1990) Size polymorphism of chicken major histocompatibility complex-encoded B-G molecules is due to length variation in the cytoplasmic heptad repeat region. Proc Natl Acad Sci U S A 87(21): 8277-81.

34. Dunon D, Kaufman J, Salomonsen J, Skjoedt K, Vainio O, Thiery JP, Imhof BA (1990) T cell precursor migration towards beta 2-microglobulin is involved in thymus colonization of chicken embryos. EMBO J 9(10): 3315-22.

35. Kaufman J, Skjoedt K, Salomonsen (1990) The MHC molecules of nonmammalian vertebrates. Immunol Rev 113: 83-117.

36. Kaufman J, Auffray C, Korman AJ, Shackelford DA, Strominger J (1984) The class II molecules of the human and murine major histocompatibility complex. Cell. 1984 Jan;36(1):1-13.

37. Kaufman J, Strominger JL (1982) HLA-DR light chain has a polymorphic N-terminal region and a conserved immunoglobulin-like C-terminal region. Nature 297(5868): 694-7.

38. Korman AJ, Knudsen PJ, Kaufman J, Strominger JL (1982) cDNA clones for the heavy chain of HLA-DR antigens obtained after immunopurification of polysomes by monoclonal antibody. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1844-8.

39. Shackelford DA, Kaufman J, Korman AJ, Strominger JL (1982) HLA-DR antigens: structure, separation of subpopulations, gene cloning and function. Immunol Rev 66: 133-87.

40. Korman AJ, Ploegh HL, Kaufman J, Owen MJ, Strominger JL (1980) Cell-free synthesis and processing of the heavy and light chains of HLA-DR antigens. J Exp Med 152(2 Pt 2): 65s-82s.

41. Kaufman J, Andersen RL, Strominger JL (1980) HLA-DR antigens have polymorphic light chains and invariant heavy chains as assessed by lysine-containing tryptic peptide analysis. J Exp Med 152(2 Pt 2): 37s-53s.

42. Engelhard VH, Kaufman J, Strominger JL, Burakoff SJ (1980) Specificity of mouse cytotoxic T lymphocytes stimulated with either HLA-A and -B or HLA-DR antigens reconstituted into phospholipid vesicles. J Exp Med 152(2 Pt 2): 54s-64s.

43. Talmadge K, Kaufman J, Gilbert W (1980) Bacteria mature preproinsulin to proinsulin. Proc Natl Acad Sci U S A. 1980 Jul;77(7): 3988-92.

44. Burakoff SJ, Engelhard VH, Kaufman J, Strominger JL (1980) Induction of secondary cytotoxic T lymphocytes by liposomes containing HLA-DR antigens. Nature 283(5746): 495-7.

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