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Torrey Pines Institute for
Molecular Studies
3550 General Atomics Court, 2-129
San Diego, CA 92121-1122
USA
Scientists
Vipin Kumar
Member
Laboratory of Autoimmunity

858.455.3870 - phone
858.455.3804 - fax

Biography

Dr. Kumar is a Member/professor and heads the Laboratory of Autoimmunity at the Institute. Dr. Kumar's research focus is on the immune regulation of “conventional” CD4 and CD8 T cells as well as on the presentation and recognition of myelin-derived glycolipids by a subset of the “non-conventional” NK T cells and their influences on autoimmune disease.

Dr. Kumar received his post-graduate training at PGIMER, Chandigarh, and a Ph.D. at the Indian Institute of Science, Bangalore in 1986. After a brief stay at the Pharmacology Dept., HSDM, Harvard University, Boston as a postdoctoral fellow, Dr. Kumar joined the Biology Dept. at California Institute of Technology, Pasadena, in 1987. In 1991, Dr. Kumar joined the Dept. of Microbiology and Molecular Genetics, UCLA where he was promoted to an Assistant Research Immunologist position in 1993.

In 1997 Dr. Kumar moved to the La Jolla Institute for Allergy and Immunology as a Research Scientist and joined Torrey Pines Institute for Molecular Studies as Associate Member in 2001 and was appointed as Member/Professor in 2003.

Dr. Kumar is currently one of the leaders in the field of immune regulation of autoimmunity. He has served as a member of special emphasis panels for the National Institutes of Health grant review study section and has served on several foreign Immunology organizations. He also has been an adhoc reviewer for a number of immunology journals, including, Nature Med., J. Exp. Med., J. Clin. Invest., and J. Immunol.

Positions and Honors

  • 1985-1987: Research Fellow, HSDM, Harvard Medical School, Boston
  • 1987-1991: Postdoctoral Research Fellow, California Institute of Technology, Pasadena
  • 1991-1993: Senior Postdoctoral Scholar, UCLA, Los Angeles
  • 1993-1997: Assistant Research Immunologist, Dept. Microbiology and Molecular Genetics, UCLA, Los Angeles
  • 1997-2002: Research Scientist, Division of Immune Regulation, LIAI, San Diego
  • 2002-2003: Associate Member, Torrey Pines Institute for Molecular Studies, San Diego
  • 2003-present: Member, Torrey Pines Institute for Molecular Studies, San Diego

Honors and Awards

  • 1971-1975 Merit Scholarship, U.P. Board, India
  • 1975-1978 Merit Scholarship, Kanpur University, India
  • 1980-1985 DST Graduate Fellowship, I.I.Sc., Bangalore, India
  • 1988-1991 Postdoctoral Fellow of the National Multiple Sclerosis Society (NMSS), USA

Research Summary

Dr. Kumar and his research team focus on a number issues related to the mechanisms involved in regulation of the T cell response. He has been investigating an important negative feedback regulatory mechanism based upon the recognition of TCR-peptide/MHC complexes by CD4 and CD8 regulatory T cells (Treg) in a model of human multiple sclerosis. His group’s effort in over past 15 years has defined a number of cellular players and their network interactions at the molecular level. He has found that CD4 Treg recognize a TCR peptide of pathogenic CD4 T cells in a class II MHC context, which then induce the recruitment of CD8 Treg, the ultimate effectors of regulation, that specifically kill the target pathogenic CD4 T cells. The CD8 Treg population has a unique phenotype in that they are CD8aa+ and recognize a different TCR peptide in the context of a non-classical class Ia molecule, Qa-1.

These studies represent the most comprehensive characterization of regulatory T cells as to their antigen specificity, MHC-restriction, TCR repertoire, as well as their mechanism of regulation at the clonal level. The laboratory is investigating the roles of these Treg populations in several diseases, including multiple sclerosis, diabetes, arthritis, and cancer to determine whether they could be potential targets for therapeutic intervention. Are CD4 and CD8 Treg primed by the pathways of cross-presentation of TCR peptides by dendritic cells following the capture of apoptotic pathogenic T cells?

Dr. Kumar’s team also has discovered a self-glycolipid ligand, sulfatide that binds to the CD1d molecule and is recognized by a distinct population within the non-conventional CD1d-restricted NK T cell subset. These NK T cells are different from the invariant a-GalCer-reactive Va14+ NK T cells. They have found that sulfatide-reactive NK T cells are enriched in the target organ (CNS) during autoimmune demyelination. They are currently investigating the interaction of these T cells with the local antigen-presenting cells in the CNS, for example microglia.

Several important issues are being addressed: what are the molecular features of the recognition of sulfatide by the CD1d and TCR; how and in which compartment is sulfatide processed and presented by CD1d molecules; is the pathway of presentation of sulfatide similar to or distinct from that of presentation of the foreign lipid, a-GalCer; is there an interaction between sulfatide-reactive and the invariant Va14+ NK T cells, and if so what are the consequences of this interaction in vivo; why do these cells normally reside in the liver? The objective of these studies is to investigate whether sulfatide—reactive T cells can be targeted to prevent and treat autoimmune diseases, including multiple sclerosis, diabetes, lupus, hepatitis as well as Alzhiemer’s.

Publications

  1. Ambrosino, E., Terabe, M., Peng, J., Takaku, S., Miyake, S., Yamamura, T., Halder, R., Kumar, V., Berzofsky, J. Cross-regulation between Type I and Type II NKT cells in regulating tumor immunity. J. Immunology, in press, 2007
  2. Halder, R., Aguilera, C., Maricic, I., Kumar, V. Type II NK T cell-mediated anergy induction in type I NK T cells prevents inflammatory liver disease. J. Clinical Invest. 117(8): 2302-12, 2007
  3. Halder, R., Jahng, A., Maricic, I., Kumar, V. Mini Review: Immune response to myelin-derived sulfatide and CNS-demyelination. Neurochem. Res. 32:257-262, 2007
  4. Smith, T., Kumar, V. A novel population of CD8aa+ regulatory T cells: Identification, characterization and induction. T cell vaccination, Eds., Drs. Zhang and Cohen, Nova Sci, 2007
  5. Smith, T., Tang, X., Kumar, V. Priming regulatory T cells and antigen-specific suppression of autoimmune disease. Immune Regulation and Immunotherapy in Autoimmune Disease, Springer,p. 20-35, 2007
  6. Tang, X., Maricic, I., Kumar, V. Anti-TCR antibody treatment activates a novel population of non-intestinal CD8aaTCRab+ Regulatory T cells and prevents experimental autoimuune encephalomyelitis. J. Immunol., 178: 6043– 6050, 2007
  7. Mayo, S., Kohler, W., Kumar, V., Quinn, A. Insulin-dependent diabetes loci Idd5 and Idd9 increase sensitivity to experimental autoimmune encephalomyelitis. Clin. Immunol. 118(2-3): 219-228, 2006.
  8. Tang, X., Maricic, I., Purohit, N., Bakamjian, B., Reed-Loisel, L., Beeston, T., Jensen, P., Kumar, V. Regulation of Immunity by a Novel Population of Qa-1-Restricted CD8 +TCR + T Cells. J. Immunol. 2006 177: 7645-7655, 2006
  9. Beeston, T., Tang, X., Maricic, I., Kumar, V. Role of Fas/FasL in regulatory T cell-mediated control of autoimmunity. FASEB Journal, 19(4):338, 2005.
  10. Genaud, S., Maricic, I., Kumar, V., Gage, F. Targeted expression of IGF-1 in central nervous system fails to protect mice from EAE. J Neuroimmunol. 168:40-5, 2005
  11. Kumar, V., Sercarz, E. Feedback regulation of autoimmunity via TCR-centered regulation. Int. Rev. Immunol. 24:199-209, 2005.
  12. Mayo, S., Kohler, W., Kumar, V., Quinn, A. Insulin-dependent diabetes loci Idd5 and Idd9 increase sensitivity to experimental autoimmune encephalomyelitis. Cell. Immunol., 18:00-00, 2005
  13. Tang, X., Maricic, I., Reed-Loisel, L., Beeston, T., Jensen, P., Kumar, V. Regulation of immunity by Qa-1-restricted CD8aa T cells. J Immunol. 177(11): 7645-7655, 2006.
  14. Tang, X., Purohit, N., Bakamjian, B., Maricic, I., Sercarz, E., Kumar, V. Identification of a CD8 T cells in immune hemeostasis. FASEB Journal, 19(4):33, 2005.
  15. Tang, X., Smith, T., Kumar, V. Specific control of immunity by regulatory CD8 T cells. Cell. Mol. Immunol. 2:11-19, 2005.
  16. Zajonc, D.M., Maricic, I., Wu, D., Halder, R., Roy, K., Wong, C.H., Kumar, V., Wilson, I.A. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J. Exp. Med. 202:1517-26, 2005.
  17. Honda, A., Ametani, A., Matsumoto, T., Iwaya, A., Kano, H., Hachimura, S., Ohkawa, K., Kaminogawa, S., Suzuki, K., Sercarz, E.E., Kumar, V. Vaccination with an immunodominant peptide of bovine type II collagen induces an anti-TCR response, and modulates the onset and severity of collagen-induced arthritis. Int. Immunol. 16:737-745, 2004.
  18. Jahng, A., Maricic, I., Aguilera, C., Cardell, S., Halder, R.C., Kumar, V. Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J. Exp. Med. 199:947-957, 2004.
  19. Kumar, V. Homeostatic control of immunity by TCR peptide-specific Tregs. J. Clin. Invest. 114:1222-1226, 2004.
  20. van den Elzen, P., Menezes, J.S., Ametani, A., Maverakis, E., Madakamutil, L., Tang, X., Kumar, V., Sercarz, E.E. Limited clonality in autoimmunity: drivers and regulators. Autoimmunity Reviews 3:524-529, 2004.
  21. Braciak, T.A., Pedersen, B., Chin, J., Hsiao, C., Ward, E.S., Maricic, I., Jahng, A., Graham, F.L., Gauldie, J., Sercarz, E.E., Kumar, V. Protection against experimental autoimmune encephalomyelitis generated by a recombinant adenovirus vector expressing the Vβ8.2 TCR is disrupted by coadministration with vectors expressing either IL-4 or -10. J. Immunol. 170:765-774, 2003.
  22. Madakamutil, L.T., Maricic, I., Sercarz, E., Kumar, V. Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes. J. Immunol. 170:2985-2992, 2003.
  23. Sercarz, E., Maverakis, E., van den Elzen, P., Madakamutil, L., Kumar, V. Seven surprises in the TCR-centred regulation of immune responsiveness in an autoimmune system. Novartis Found. Symp. 252:165-171, 2003.
  24. Maverakis, E., Beech, J., Deng, H., Schneider, S., Van den Elzen, P., Madakamutil, L., Ria, F., Moudgil, K., Kumar, V., Campagnoni, A., Sercarz, E.E. Determination of the expressed repertoire: the outcome of competition at all levels of antigen presentation and TCR recognition. In: Epitope recognition since Landsteiner's discovery: Springer Publications, Chapter 4, 2002.
  25. Singh, R.R., Ebling, F.M., Albuquerque, D.A., Saxena, V., Kumar, V., Giannini, E.H., Marion, T.N., Finkelman, F.D., Hahn, B.H. Induction of autoantibody production is limited in non-autoimmune mice. J. Immunol. 169:587-594, 2002.
  26. Jahng, A.W., Maricic, I., Pedersen, B., Burdin, N., Naidenko, O., Kronenberg, M., Koezuka, Y., Kumar, V. Activation of natural killer T cells potentiates or prevents experimental autoimmune encephalomyelitis. J. Exp. Med. 194:1789-1799, 2001.
  27. Kumar, V. The beginning of a journey into physiological regulation of autoimmunity. In: Autoimmunity and emerging diseases, L. Steinman Ed., p118-130, 2001.
  28. Kumar, V., Maglione, J., Thatte, J., Pedersen, B, Sercarz, E., Ward, E.S. Induction of a type 1 regulatory CD4 T cell response following Vβ8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis. Intl. Immunol. 13:835-841, 2001.
  29. Kumar, V., Sercarz, E. An integrative model of regulation centered on recognition of TCR peptide/MHC complexes. Immunol. Reviews 182:113-121, 2001.
  30. Kumar, V., Sercarz, E., Zhang, J, Cohen, I. T cell vaccination: from basics to the clinic. Trends in Immunology 22:539-540, 2001.
  31. Quinn, A., Kumar, V., Jensen, K., Sercarz, E. Interactions of effectors and regulators are decisive in the manifestation of IDDM in NOD mice. Molecular pathology of Type 1 diabetes mellitus. Curr. Dir. Autoimmun. 4:171-192, 2001.
  32. Wilson, S.S., van den Elzen, P., Maverakis, E., Beech, J.T., Braciak, T.A., Kumar, V., Sercarz, E. Residual public repertoires to self. J. Neuroimmunol. 107:233-239, 2000.
  33. Kumar, V., Sercarz, E. Distinct levels of regulation in organ-specific autoimmune diseases. Life Sci. 65:1523-1530, 1999.
  34. Borghans, J.A.M., De Boer, R.J., Sercarz, E., Kumar, V. T cell vaccination in experimental autoimmune encephalomyelitis: a mathematical model. J. Immunol. 161:1087-1093, 1998.
  35. Kumar, V. Determinant spreading during experimental autoimmune encephalomyelitis: is it potentiating, protecting, or participating in the disease. Immunological Rev. 164:73-80, 1998.
  36. Kumar, V. TCR peptide-reactive T cells and peripheral tolerance to myelin basic protein. Research in Immunol. 149:827-834, 1998.
  37. Kumar, V., Sercarz, E. Induction or protection from autoimmune disease depends upon the cytokine secretion profile of TCR peptide specific CD4 T cells. J. Immunol. 161:6585-6591, 1998.
  38. Kumar, V., Sercarz, E., Adorini, L. Regulatory mechanisms in organ-specific autoimmunity. Immunologist. 6:161-166, 1998.
  39. Kumar, V., Aziz, F., Sercarz, E., Miller, A. Regulatory T cells specific for the same framework 3 region of the V?8.2 chain are involved in the control of collagen II-induced arthritis and experimental autoimmune encephalomyelitis. J. Exp. Med. 185:1725-1733, 1997.
  40. Kumar, V., Coulsell, E., Hubbard, G., Ober, B., Sercarz, E., E., Ward, E.S. Recombinant single chain TCR molecules can prevent and reverse experimental autoimmune encephalomyelitis. J. Immunol. 159:5150-5156, 1997.
  41. Kumar, V., Sercarz, E. Structure of the antigenic determinant or the execution of T cell regulatory circuitry can result in immune deviation. In: Th1/Th2 regulation, Landes Inc., pp 91-103, 1997.
  42. Kumar, V., Moudgil, K.D., Singh, R.R., Sercarz, E.E. Protected repertoires, the cryptic self and autoimmunity. In: New Trends in Immunological diseases. Acad. Press, p49-59, 1996.
  43. Kumar, V., Sercarz, E. Dysregulation of potentially pathogenic self-reactivity is crucial for the manifestation of clinical autoimmunity. J. Neurosci. Res. 45:334-339, 1996.
  44. Kumar, V., Sercarz, E. Genetic vaccination: the advantages of going naked. Nature Med. 2:11-12, 1996
  45. Kumar, V., Stellrecht, K., Sercarz, E. Inactivation of TCR peptide-specific regulatory CD4 T cells leads to chronic EAE. J. Exp. Med. 184:1609-1617, 1996.
  46. Sercarz, E., Deng, H., Grewal, I., Kumar, V., Moudgil K. T cell repertoire directed against dominant and cryptic self-determinants. In: Transplantation tolerance induction, Landes Co. p111-117, 1996.
  47. Kumar, V., Bhardwaj, V., Soares, L., Alexander, J., Sette, A., Sercarz, E. MHC-ligand affinity of an antigenic determinant is crucial for differential secretion of IFN-? or IL-4 by T cells. Proc. Natl. Acad. Sci. USA. 92:9510-9514, 1995.
  48. Kumar, V., Sercarz, E. Natural priming of functional TCR-peptide-specific T cells indicates that TCR determinants are involved in the regulation of autoimmune disease. In: T cell vaccination and autoimmune disease, Eds., J. Zhang and J. Raus, R.G. Landes Company, Austin, pp 21-35, 1995.
  49. Kumar, V., Tabibiazar, R., Geysen, M., Sercarz, E. Immunodominant framework region 3 peptide from TCR V?8.2 chain controls murine experimental autoimmune encephalomyelitis. J. Immunol. 154:1941-1950, 1995.
  50. Singh, R.R., Kumar, V., Ebling, F., Southwood, S., Sette, A., Sercarz, E., Hahn, B.H. T cell determinants from autoantibodies to DNA can upregulate autoimmunity in murine lupus. J. Exp. Med. 181:2017-2027, 1995.
  51. Soares, L., Deng, H., Grewal, I.S., Kumar, V., Miller, A., Moudgil, K., Palmer, M., Sercarz, E. Determinant flanking regions and the design of appropriate vaccines. Annals NY Acad. Sci. 754:48-56, 1995.
  52. Bhardwaj, V., Kumar, V., Grewal, I., Dao, T., Lehmann, P. Geysen, M., Sercarz, E. The T cell determinant structure of myelin basic protein in B10.PL, SJL, and their F1s. J. Immunol. 152:3711-3719, 1994.
  53. Kumar, V., Bhardwaj, V., Sercarz, E. T cell recognition of defined peptides and autoimmune response. In: Handbook of T and B cells. Ed. C.C. Snow, Academic Press, pp 269-287, 1994.
  54. Kumar, V., Sercarz, E. Holes in the T cell repertoire to MBP owing to the absence of the D?2-J?2 gene cluster: Implications for TCR recognition and autoimmunity. J. Exp. Med. 179:1637-1643, 1994.
  55. Kumar, V., Sercarz, E. Maintenance and re-establishment of self-tolerance: TCR-peptide-specific regulatory T cells. In: Autoimmunity: Experimental aspects. Ed. M. Zouali, Springer-Verlag. Berlin, pp 29-38, 1994.
  56. Kumar, V., Sercarz, E. Self-determinant selection and selective regulation. Chem. Immunol. 60:1-19, 1994.
  57. Bhardwaj, V., Kumar, V., Geysen H.M., Sercarz, E. Degenerate recognition of a dissimilar antigenic peptide by MBP-reactive T cells: Implications for thymic education and autoimmunity. J. Immunol. 151:5000-5011, 1993.
  58. Kumar, V., Sercarz, E. The involvement of TCR-peptide-specific regulatory CD4+ T cells in recovery from antigen-induced autoimmune disease. J. Exp. Med. 178:909-916, 1993.
  59. Moudgil, K.D., Ametani, A., Grewal, I.S., Kumar, V., Sercarz, E.E. Processing of self-proteins and its impact on shaping the T cell repertoire, autoimmunity and immune regulation. Int. Rev. Immunol. 10:365-377, 1993.
  60. Bhardwaj, V., Kumar, V., Geysen, H.M., Sercarz, E. Subjugation of dominant immunogenic determinants within a chimeric peptide. Eur. J. Immunol. 22:2009-2016, 1992.
  61. Kumar, V., Sercarz, E. T cell regulatory circuitry: Antigen-specific and TCR-idiopeptide specific T cell interactions in EAE. Intl. Rev. Immunol. 9: 269-279, 1992.
  62. Bhardwaj, V., Kumar, V., Lehmann, P.V., Sercarz, E. Mimicry and dominance in the T cell response to self proteins. In: Lymphatic Tissues and In Vivo Immune Responses. Eds., Ezine, S., S Berrih-Aknin and B. Imhof, Marcel Dekker Inc., New York, 1991.
  63. Burns, J., Littlefield, K., Gomez, C., Kumar, V. Assessment of antigenic determinants for the human T-cell response against myelin basic protein using overlapping synthetic peptides. J. Neuroimmunology 31:265-272, 19991.
  64. Kumar, V., Sercarz, E. Regulation of autoimmune disease. Current Opinion in Immunology 3:888-895, 1991.
  65. Zhang, Z., Kumar, V., Rivera, R., Chisholm, J., Biswas, D.K. Cis-acting negative regulatory element of prolactin gene. J. Biol. Chem. 65:4785-4788, 1990.
  66. Hood, L., Kumar, V., Osman, G., Beall, S.S., Gomez, C., Funkhouser, W., Kono, D.H., Nickerson, D., Zaller, D.M., Urban, J. Autoimmune disease and T-cell immunologic recognition. Cold Spring Harbor Symposium of Quantitative Biology, LIV:859-874, 1989.
  67. Kumar, V., Kono, D.H., Urban, J.L., Hood. L. T-cell receptor repertoire and autoimmune diseases. Ann. Rev. Immunol. 7:657-682, 1989.
  68. Urban, J.L., Kumar, V., Kono, D.H., Gomez, C., Hood, L. T-cells receptors in experimental allergic encephalomyelitis. In: Neuroimmune Networks: Physiology and Disease, Ed., E. Goetzl, Alan R. Liss Inc., pp. 25-30, 1989.
  69. Zhang, Z., Kumar, V., Rivera, R., Pasion, G., Chisholm, J., Biswas, D.K. Suppression of prolactin gene expression in GH cells correlates with site-specific DNA methylation. DNA. 8:605-613, 1989.
  70. Kumar, V., Biswas, D.K. Dynamic state of site-specific DNA methylation concurrent to altered prolactin and growth hormones gene expression in the pituitary gland of pregnant and lactating rats. J. Biol. Chem. 263:12645-12652, 1988.
  71. Urban, J., Kumar, V., Kono, D., Gomez, C., Horvath, S.J., Clayton, J., Ando, D., Sercarz, E., Hood, L. Restricted use of TCR V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy. Cell 54:577-592, 1988.
  72. Kumar, V., Biswas, D.K. Defective regulatory elements at the 5' upstream of rat prolactin gene of steroid non-responsive GH subclone. Biochim. Biophys. Acta. 910:213-223, 1987.
  73. Kumar, V., Kurup, C.K.R. Interaction of lutein with mitochondrial and artificial membranes. In: Current Trends in Life Sciences, III Biomembranes: Structure, Biogenesis and Transport. Eds., C. Rajamanickam and L. Packer, pp. 145-153, 1987.
  74. Pasion, S., Kumar, V. and Biswas, D.K. DNA sequences responsible for the drug-induced amplification of prolactin gene. DNA:16, 419-428, 1987.
  75. Kumar, V., Kurup, C.K.R. Interaction of lutein with phosphatidylcholine bilayers. Biochim. Biophys. Acta. 860:286-292, 1986.
  76. Kumar, V., Kurup, C.K.R. Effect of lutein on the transport of calcium across phospholipid bilayer and mitochondrial membrane. Biochemistry Intl., USA 12:373-377, 1986.
  77. Kumar, V., Kurup, C.K.R. Purification, characterization and mode of action of a regulatory factor of mitochondrial oxidative phosphorylation from plant chloroplasts. Ind. J. Biochem. Biophys. 23:156-161, 1986.
  78. Kumar, V., Kurup, C.K.R. Regulation of mitochondrial oxidative phosphorylation by chloroplasts. Curr. Sci. 54:550-553, 1985.
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