Lymphotoxin: Cloning, Regulation and Mechanism of Killing

  1. Gregory Bock Organizer and
  2. Joan Marsh
  1. Nancy H. Ruddle1,
  2. Chang-Ben Li1,
  3. Wei-Liang Tang1,
  4. Patrick W. Gray2 and
  5. Katherine M. McGrath1

Published Online: 28 SEP 2007

DOI: 10.1002/9780470513521.ch6

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins

How to Cite

Ruddle, N. H., Li, C.-B., Tang, W.-L., Gray, P. W. and McGrath, K. M. (2007) Lymphotoxin: Cloning, Regulation and Mechanism of Killing, in Ciba Foundation Symposium 131 - Tumour Necrosis Factor and Related Cytotoxins (eds G. Bock and J. Marsh), John Wiley & Sons, Ltd., Chichester, UK. doi: 10.1002/9780470513521.ch6

Author Information

  1. 1

    Department of Epidemiology & Public Health, Yale University School of Medicine, 60 College Street, PO Box 3333, New Haven, Connecticut 06510, USA

  2. 2

    Genentech Inc., 460 Point San Bruno Boulevard, South San Francisco, California 94080, USA

Publication History

  1. Published Online: 28 SEP 2007

ISBN Information

Print ISBN: 9780471910978

Online ISBN: 9780470513521

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Keywords:

  • lymphotoxin;
  • cloning;
  • regulation;
  • mechanism killing;
  • T cell receptors

Summary

The gene for murine lymphotoxin (MuLT) has been cloned from a cDNA library prepared using poly(A)+ RNA from an activated murine IL-2-maintained cloned T cell line (21C11). This was accomplished with a MuLT BarnHI fragment isolated from a murine genomic library by hybridization to a human LT cDNA probe. Northern blot analysis with RNA from 21C11, an L3T4+ (CD4+-equivalent) ovalbumin-specific class II-restricted T cell line, revealed a 15S band that hybridized to this MuLT fragment. A cDNA library prepared with poly(A)+ RNA from 21C11 cells contained 36 colonies that hybridized with the MuLT BarnHI fragment. A full-length cDNA has been isolated, sequenced, expressed in COS–1 cells and used to map MuLT to mouse chromosome 17. The sequence and structure of the MuLT gene has been determined. MuLT cDNA has been used to analyse mRNA expression in several L3T4+ and Lyt-2+ (CD8+-equivalent) T cell clones activated with antigen, mitogen, or antibody to the T cell receptor. LT is expressed by both class I- and class II-restricted T cells. The mechanism of killing by both LT and the functionally related molecule TNF-α includes the induction of DNA fragmentation in the target cell.