I was intrigued by the mechanisms of immunity, especially generation of diversity (GOD), that protect but are tolerant to ‘self’ at the same time. The loss of tolerance, however, leads to development of autoimmune disease occasionally. While in France, United States and Switzerland, our research on construction and regulation of immune system in health and disease demonstrated that same genetic elements of the immune system, earlier identified by us, that defended host against harmful agents also generated pathogenic ‘autoantibodies’ responsible for autoimmune diseases. Our laboratory also demonstrated that B-cell selection during development influences generation of pathogenic autoantibodies. Studies of the construction of immune system across species led us to examine the bovine immune system that has limited germline diversity, but this species employs alternate strategies, for example, exceptionally long CDR3H, for antibody diversification. Our research focuses on basic and functional aspects of antibody engineering, e.g., construction of single chain Fv (scFv) relevant to immunodiagnosis and therapy. Other studies involve autoimmunity and clinical veterinary immunology. (Kaushik Laboratory).
D.Sc. (Tres Honorable) Inst. Pasteur, Paris
Immunology: Autoimmunity and systemic autoimmune disease, Molecular immunoglobulin genetics, Antibody transgenesis, Immunotherapy and Immunodiagnostics.
Koti, M., Nagy, E. and Kaushik, A. K. 2011. A single point mutation in framework region 3 of heavy chain affects viral neutralization dynamics of single-chain Fv against bovine herpes virus type 1. Vaccine. 29: 7905-7912.
Koti, M., W. Farrugia, E. Nagy, P. A. Ramsland, and A. K. Kaushik. 2010. Construction of single-chain Fv with two possible CDR3H conformations but similar inter-molecular forces that neutralize bovine herpesvirus 1. Mol Immunol 47:953-960.
Pasman, Y., S. S. Saini, E. Smith, and A. K. Kaushik. 2010. Organization and genomic complexity of bovine lambda-light chain gene locus. Vet Immunol Immunopathol 135:306-313.
Koti, M., G. Kataeva, and A. K. Kaushik. 2010. Novel atypical nucleotide insertions specifically at VH-DH junction generate exceptionally long CDR3H in cattle antibodies. Mol Immunol 47:2119-2128.
Kaushik, A. K., Kehrlis Jr., M. E., Ng, S., Kurtz, A., Koti, M., Shojaei, F. Saini, S. 2009. Somatic mutations and isotype restricted exceptionally long CDR3H contribute to antibody diversification in cattle. Vet. Immunol. Immunopathol. 127:106-13.
Koti, M., Kataeva, G. and Kaushik, A. K. 2008. Organization of DH-gene locus is distinct in cattle. Dev. Biol. (Basel) 132:307-13.
Saini, S.S., Farrugia W., Muthusamy N., Ramsland, P. A. & Kaushik, A.K. 2007. Structural evidence for a new IgG1 antibody sequence allele of cattle. Scandinavian Journal of Immunology. 65:32-38.
Cassady, R.L. and Kaushik, A. K. 2006. Increased negative B cell selection impairs neonatal B cell repertoire but does not directly lead to generation of disease associated IgM autoantibodies. International Immunology. 18:661-69 (Supplementary figure S1 and tables S1-4 online).
Shojaei F, Saini SS, Kaushik AK. Unusually long germline DH genes contribute to large sized CDR3H in bovine antibodies. Molecular Immunology. 40(1): 61-7, September 2003
Saini SS, Farrugia W, Ramsland PA, Kaushik AK. Bovine IgM antibodies with exceptionally long complementarity-determining region 3 of the heavy chain share unique structural properties conferring restricted V(H) + V(lambda) pairings. International Immunology. 15(7): 845-53, July 2003
Saini SS, Kaushik A. Extensive CDR3H length heterogeneity exists in bovine fetal VDJ rearrangements. Scandinavian Journal of Immunology. 55(2): 140-8, February 2002
Kaushik, A. and Bona, C.. Genetic Origin of Murine Autoantibodies. The Molecular Pathology of Autoimmune Diseases. (Taylor and Francis,): pp. 53-67, 2002
Saini SS, Kaushik A. Origin of bovine IgM structural variants. Molecular Immunology. 38(5): 389-96, September 2001
Ramsland PA, Kaushik A, Marchalonis JJ, Edmundson AB. Incorporation of long CDR3s into V domains: implications for the structural evolution of the antibody-combining site. Experimental and Clinical Immunogenetics. 18(4): 176-98, 2001
“Novel bovine VDJ cassette, BF1H1, suitable for antigenization”, U.S. Patent, No. 6,740,747; Canadian Patent No. 2382766.
“Bovine D-genes and their application”, US patent No. 7,196,185 .
“Development of neutralizing ScFvs against Bovine Herpes Virus type-1 for prevention, therapy and diagnosis of Infectious Bovine Rhino-tracheitis (PCT International Patent Application filed July, 2008)
MICR*3230 Immunology I
MICR*4530 Immunology II
Yfke Pasman (Ph.D.)
Comparative Immunoglobulin Workshop (CIgW)
At Guelph article