Abstract

We propose to study diversity, somatic reorganization, and expression of mouse Ig genes. Using the recombinant DNA technique, we will clone a variety of DNA fragments containing the Ig genes and their flanking sequences and characterize these DNA clones by various methods including heteroduplex analysis, R loop analysis, restriction enzyme mapping and DNA sequencing. As the sources of cells we will use myelomas, hybridomas representing various stages of B cell differentiation and natural B lymphocytes fractionated by a fluorescence-activated cell sorter. We will also identify and characterize enzymes responsible for somatic recombinations. Our goal is to decipher at the molecular level the genetic mechanisms that are responsible for the vast antibody diversity and the expression of Ig genes including allelic exclusion, heavy chain switch and simultaneous synthesis of two heavy chain classes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI017879-05
Application #
3127482
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1981-06-01
Project End
1986-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code

  Publications

Eichelberger, M; McMickle, A; Blackman, M et al. (1995) Functional analysis of the TCR alpha- beta+ cells that accumulate in the pneumonic lung of influenza virus-infected TCR-alpha-/- mice. J Immunol 154:1569-76
Levelt, C N; Mombaerts, P; Wang, B et al. (1995) Regulation of thymocyte development through CD3: functional dissociation between p56lck and CD3 sigma in early thymic selection. Immunity 3:215-22
Ashton-Rickardt, P G; Bandeira, A; Delaney, J R et al. (1994) Evidence for a differential avidity model of T cell selection in the thymus. Cell 76:651-63
Holland, G D; Ito, K; Kaehler, D A et al. (1991) Thymic targets for Abelson murine leukemia virus are early gamma/delta T lymphocytes. Proc Natl Acad Sci U S A 88:3700-4
Kappes, D J; Browne, C P; Tonegawa, S (1991) Identification of a T-cell-specific enhancer at the locus encoding T-cell antigen receptor gamma chain. Proc Natl Acad Sci U S A 88:2204-8
Van Kaer, L; Wu, M; Ichikawa, Y et al. (1991) Recognition of MHC TL gene products by gamma delta T cells. Immunol Rev 120:89-115
Bonneville, M; Itohara, S; Krecko, E G et al. (1990) Transgenic mice demonstrate that epithelial homing of gamma/delta T cells is determined by cell lineages independent of T cell receptor specificity. J Exp Med 171:1015-26
Ito, K; Van Kaer, L; Bonneville, M et al. (1990) Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor. Cell 62:549-61
Bonneville, M; Ito, K; Krecko, E G et al. (1989) Recognition of a self major histocompatibility complex TL region product by gamma delta T-cell receptors. Proc Natl Acad Sci U S A 86:5928-32
Takagaki, Y; Nakanishi, N; Ishida, I et al. (1989) T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. J Immunol 142:2112-21

Showing the most recent 10 out of 21 publications