HISTORY OF RESEARCH

The Department of Immunology is the oldest freestanding Immunology Department in the country, formed as a basic science department as part of the inception of Mayo Medical School in the early 1970's under the leadership of Dr. Thomas Tomasi. Dr. Tomasi recruited a multidisciplinary group of five junior to mid career independent investigators (Drs. Atassi, David, Fathman, McKean, and Steinmuler) with expertise in cellular immunology, biochemistry, and mammalian genetics to investigate fundamental principles underlying the unique biological properties of the immune system. Among the important questions being addressed at that time were the physical nature of antigens, basic mechanisms of antigen recognition, and the genetic basis of differential capacity to generate immune responses. All six Immunology laboratories were very successful, establishing strong publication records and developing expertise and reputations in basic immunology that were recognized around the world. By the early 1980's this group of immunology investigators was well recognized for their biochemical perspectives on immune functions and their progress in determining the molecular basis of T cell recognition of antigens.

Over the past thirty years members of the Department of Immunology have made significant scientific contributions. Listed below are some key discoveries attributed to Mayo investigators with primary appointments in Immunology.

1. Fathman laboratory: Development of T cell clones that ultimately led to the definition of T cell epitopes.
2. Steinmuller laboratory: Identification of the primary antigens in the skin and their immunodominant role in determining the outcome of skin transplantation.
3. Steinmuller laboratory: Description of passenger leuckocytes and their importance in tissue grafts.
4. Atassi laboratory: Definition of the biochemical nature of antigens targeted by antibodies and T cells using peptides.
5. Gleich laboratory: The identification of key effector molecules used by eosinophils in anti-parasite responses and their importance in the pathogenesis of asthma.
6. Lennon laboratory: The characterization of a series of human autoantibodies and their association with underlying pathologies associated with paraneoplastic autoimmunity.
7. Lennon laboratory: Development of clinical diagnostic application of ability to identify specific autoimmune antibodies in patient serum.
8. David laboratory: Identification of the molecular basis of immune response gene function and initial genetic and biochemical characterizations of class II MHC molecules.
9. David laboratory: Developed widely used, genetically defined MHC recombinant mouse strains used extensively around the world.
10. David laboratory: The development of several important experimental mouse models of autoimmune disease, including a series of transgenic/knockout mice that express humanized MHC.
11. McKean laboratory: The identification of structural changes that occur in antibodies during somatic maturation of antibody affinity.
12. McKean laboratory: The characterization of the role of MHC class II diversity in antigen presentation to T cells.
13. Pease laboratory: Identification of mechanisms that lead to MHC class I diversity and the structural significance of that diversity for antigen-presenting function.
14. Pease laboratory: Identification of a key peptide used to determine the crystal structure of the first T cell receptor:MHC class I complex, defining this key molecular interaction governing immune recognition.
15. Pease laboratory: Development of a novel strategy for engineering DNA, a PCR-based procedure the revolutionized DNA engineering and is now widely used around the world.
16. Pease laboratory: Development of recombinant human IgM antibodies for that can target and modulate cells in vivo.
17. Pease laboratory: Development of a novel, powerful adjuvant using IgM antibodies specific for mouse and human dendritic cells. This antibody has immunotherapeutic potential as shown using experimental model system in which established tumors were cured and allergic asthma blocked.
18. Leibson laboratory: Development of strategies for cloning human NK cells.
19. Leibson laboratory: Identification of signaling pathways that regulate NK cell killing.
20. Abraham laboratory: Developed a series of mutant, human T cells that have been used extensively to identify key signaling components critical for T cell activation following T cell receptor-mediated activation.
21. Abraham laboratory: Provided key insights into the immunosuppressive properties of rapamycin.
22. Abraham laboratory: Identified MTOR (mammalian target of rapamycin) as a key mammalian regulator of cell growth. This observation has led to a new form of stent used to open blocked cardiac blood vessels.
23. Jelinek laboratory: Generation of a panel of human myeloma cell lines exhibiting a spectrum of disease-relevant phenotypes. These cell lines have been broadly used by investigators at Mayo and by other institutions to study basic molecular and cellular mechanisms intrinsic to malignant plasma cells.
24. Jelinek laboratory: Elucidation of the molecular mechanisms of action of various cytokines in human B lymphocyte malignancies, e.g., interleukin 6, oncostatin-M, interferon-alpha, insulin-like growth factor. In some cases, these observations have contributed to forming the rationale to clinically target given molecules in disease, e.g., insulin-like growth factor.
25. Jelinek laboratory: Demonstration of the importance of leukemic B cell expression of the CD38 molecule and extent of immunoglobulin variable region somatic mutations to disease progression in B cell chronic lymphocytic leukemia (B-CLL) patients entered onto clinical trials. 
26. Jelinek laboratory: First demonstration of autocrine BLyS and APRIL expression by chronic lymphocytic leukemia B cells and myeloma cells, and characterization of receptor expression profiles. Currently, there is intense pharmaceutical interest in targeting BLyS and/or APRIL or their receptors in patients with B cell malignancies, and this work provided some of the foundation for this interest.
27. Jelinek laboratory: Identification of a global and disease progression-specific genetic signature exhibited by chronic lymphocytic leukemia B cells. This information provides a warehouse of information that can fuel future mechanistic studies and suggest new therapeutic targets.
28. Chen laboratory: Identification of new co-stimulatory molecules that govern T cell responses and tolerance. One of these molecules, B7-H1, has immune inhibitory properties and is now known to be expressed by tumor cells. Its expression has recently been associated with the prognosis of renal cell carcinoma by Mayo investigators. B7-H1 may be a useful target for antibody blockade as an intervention against a novel tumor escape mechanism.
29. Chen laboratory: Development of antibodies for manipulating T cell responses by engaging co-stimulatory molecules for the purpose of immunotherapy. A humanized antibody with binding specificity for the costimulatory molecule 4-1BB is being developed for clinical trial. This molecule strongly enhances T cell antitumor responses and can break tolerance under certain conditions.
30. Celis laboratory: Development of strategies using the TLR-9 ligand CpG-ODN to induce anti-peptide T cell responses.
31. Celis laboratory: Invention of the "Trojan" peptide delivery system for efficiently introducing peptide antigens into antigen presenting cells.
32. Celis laboratory: Identification of novel tumor antigens shared by different kinds of human cancer cells. Several clinical trials have been initiated using these peptide antigens.