We are studying the interaction of mouse T-helper cells, T-suppressor cells, B cells, and macrophages in the immune response to two proteins, lysozyme and beta-galactosidase. Our overall objective is to ascertain whether there are differences among these cell types in epitope recognition. Earlier evidence has shown us that key suppressive determinants exist on these two proteins. We will study how the presentation of antigen by macrophages influences the T-cell recognition, what specificities are characteristic of T-helper and T-suppressor subpopulations and how this compares with B cell populations, and how the nature of the immune response is altered by separating suppressor from helper determinants, or by fracturing or covering suppressive determinants. We will study the effect of anti-idiotypic antibodies raised against B-cell hybridomas and T cell hybridomas of defined specificity (anti-lysozyme and anti-beta galactosidase) in shifting the regulatory balance. We would like to clarify the crossover between idiotypic and antigenic regulatory universes. The cellular target of suppressor cells will be defined. The major assay system to be employed are in vitro T-dependent antibody forming systems where our protein antigens act as carriers for anti-hapten responses, and antigen-dependent T-proliferation systems using primed lymph nodes and peritoneal-exudate T cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI011183-13
Application #
3124906
Study Section
Immunobiology Study Section (IMB)
Project Start
1978-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
13
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Arts and Sciences
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Melo, Marco E F; Gabaglia, Claudia Raja; Moudgil, Kamal D et al. (2002) Strain-dependent effect of nasal instillation of antigen on the immune response in mice. Isr Med Assoc J 4:902-7
Moudgil, K D; Kim, E; Yun, O J et al. (2001) Environmental modulation of autoimmune arthritis involves the spontaneous microbial induction of T cell responses to regulatory determinants within heat shock protein 65. J Immunol 166:4237-43
Schneider, S C; Ohmen, J; Fosdick, L et al. (2000) Cutting edge: introduction of an endopeptidase cleavage motif into a determinant flanking region of hen egg lysozyme results in enhanced T cell determinant display. J Immunol 165:20-3
Kang, H K; Mikszta, J A; Deng, H et al. (2000) Processing and reactivity of T cell epitopes containing two cysteine residues from hen egg-white lysozyme (HEL74-90). J Immunol 164:1775-82
Moudgil, K D; Sercarz, E E (2000) The self-directed T cell repertoire: its creation and activation. Rev Immunogenet 2:26-37
Moudgil, K D; Southwood, S; Ametani, A et al. (1999) The self-directed T cell repertoire against mouse lysozyme reflects the influence of the hierarchy of its own determinants and can be engaged by a foreign lysozyme. J Immunol 163:4232-7
Gabaglia, C R; Pedersen, B; Hitt, M et al. (1999) A single intramuscular injection with an adenovirus-expressing IL-12 protects BALB/c mice against Leishmania major infection, while treatment with an IL-4-expressing vector increases disease susceptibility in B10.D2 mice. J Immunol 162:753-60
Borghans, J A; De Boer, R J; Sercarz, E et al. (1998) T cell vaccination in experimental autoimmune encephalomyelitis: a mathematical model. J Immunol 161:1087-93
Moudgil, K D; Wang, J; Yeung, V P et al. (1998) Heterogeneity of the T cell response to immunodominant determinants within hen eggwhite lysozyme of individual syngeneic hybrid F1 mice: implications for autoimmunity and infection. J Immunol 161:6046-53
Sercarz, E E (1998) Immune focusing vs diversification and their connection to immune regulation. Immunol Rev 164:5-10

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