The overall aim of this study is to determine the requirements necessary for activation of T-lymphocytes in response to mitogens and antigens. These studies will be undertaken using a unique haplotype-dependent, T-cell mitogen derived from Mycoplasma arthritidis. More specifically, our research is directed toward the following aims: 1) Purification and characterization of the T-cell mitogen derived from M. arthritidis. 2) Accessory cell requirements for presentation of mitogen and antigen to T-lymphocytes and role of soluble mediators. 3) Differential accessory cell requirements for activation of T-cells, T-hybridomas and T-cell clones. 4) Mechanisms of T-cell recognition of processed mitogen and antigens. 5) Mechanisms and gene control of non-MHC factors in mice and rats which suppress responsiveness to mitogens and antigens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI012103-12
Application #
3125111
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1978-03-01
Project End
1990-02-28
Budget Start
1988-03-01
Budget End
1989-02-28
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
Schools of Medicine
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Mu, Hong-Hua; Humphreys, Jennifer; Chan, Fok Vun et al. (2006) TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis. Cell Microbiol 8:414-26
Mu, H-H; Pennock, N D; Humphreys, J et al. (2005) Engagement of Toll-like receptors by mycoplasmal superantigen: downregulation of TLR2 by MAM/TLR4 interaction. Cell Microbiol 7:789-97
Mu, H H; Sawitzke, A D; Cole, B C (2001) Presence of Lps(d) mutation influences cytokine regulation in vivo by the Mycoplasma arthritidis mitogen superantigen and lethal toxicity in mice infected with M. arthritidis. Infect Immun 69:3837-44
Mu, H H; Sawitzke, A D; Cole, B C (2000) Modulation of cytokine profiles by the Mycoplasma superantigen Mycoplasma arthritidis mitogen parallels susceptibility to arthritis induced by M. arthritidis. Infect Immun 68:1142-9
Cole, B C (1999) Mycoplasma-induced arthritis in animals: relevance to understanding the etiologies of the human rheumatic diseases. Rev Rhum Engl Ed 66:45S-49S
Cole, B C; Sawitzke, A D; Ahmed, E A et al. (1997) Allelic polymorphisms at the H-2A and HLA-DQ loci influence the response of murine lymphocytes to the Mycoplasma arthritidis superantigen MAM. Infect Immun 65:4190-8
Knudtson, K L; Manohar, M; Joyner, D E et al. (1997) Expression of the superantigen Mycoplasma arthritidis mitogen in Escherichia coli and characterization of the recombinant protein. Infect Immun 65:4965-71
Cole, B C; Knudtson, K L; Oliphant, A et al. (1996) The sequence of the Mycoplasma arthritidis superantigen, MAM: identification of functional domains and comparison with microbial superantigens and plant lectin mitogens. J Exp Med 183:1105-10
Atkin, C L; Wei, S; Cole, B C (1994) The Mycoplasma arthritidis superantigen MAM: purification and identification of an active peptide. Infect Immun 62:5367-75
Griffiths, M M; Cole, B C; Ito, J et al. (1993) T-cell receptors and collagen induced arthritis in H-2r mice. Autoimmunity 14:221-9

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