This program project is aimed at understanding the molecular basis of signalling B and T lymphocytes to become activated and differentiate. A multi-disciplinary effort utilizing molecular genetics, cell cloning technology, flow cytometry and protein chemistry will be utilized for the experiments. Thus, a number of T cell-derived lymphokines and their receptors on B lymphocytes are currently being isolated and characterized using monoclonal antibodies, protein chemistry and/or molecular genetics. Using these reagents, the mechanisms underlying activation of B lymphocytes and cytotoxic T lymphocyte precursors are being elucidated. The mechanisms underlying isotype switch in B lymphocytes are being studied by isolating cell populations that preferentially change isotype synthesis from IgM to particular subclasses of IgG. For the study of the generation of cytotoxic T cells (CTL), we will utilize recombinant inbred strains of mice in order to determine the genetic requirements for T help in the induction of CTL. Exon shuffling experiments using MHC products as well as MHC mutants will aid in the determination of structure-function relationships. We will investigate the role of the C2 domain of class I MHC molecules in delivering an activating signal to cytotoxic T lymphocytes (CTL). In order to determine the role of the C2 domain, we will analyze L cells transfected with mouse-human (hybrid) class I genes. We will determine the role of immune response genes in secondary CTL responses in vitro by assaying the ability of (B6 x bm12)F1 animals to respond in vitro to the H-Y alloantigen.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI011851-14
Application #
3091425
Study Section
Transplantation and Immunology Committee (TIC)
Project Start
1974-03-01
Project End
1989-04-30
Budget Start
1987-05-01
Budget End
1988-04-30
Support Year
14
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Overall Medical
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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