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J. Biol. Chem., Vol. 277, Issue 7, 5040-5046, February 15, 2002
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From the Norris Comprehensive Cancer Center, Departments of
Pathology, Biochemistry & Molecular Biology, Molecular Microbiology
& Immunology, and Biological Sciences, University of Southern
California, Keck School of Medicine, Los Angeles, California
90089-9176
The human immunoglobulin heavy chain locus
contains 39 functional human VH elements. All 39 VH elements (with their adjacent heptamer/nonamer signal)
were tested for site-specific cleavage with purified human core RAG1
and RAG2, and HMG1 proteins in a 12/23-coupled cleavage reaction. Both
nicking and hairpin formation were measured. The individual
VH cleavage efficiencies vary over nearly a 30-fold range.
These measurements will be useful in considering the factors affecting
the generation of the immunoglobulin and T-cell receptor repertoires in
the adult humans. Interestingly, when these cleavage efficiencies are
summed for each of the VH families, the six VH
family efficiencies correspond closely to the observed profile of
unselected VH family usage in the peripheral B cells of
normal adult humans. This correspondence raises the possibility that
the dominant factor determining VH element utilization within the 1-megabase human genomic VH array is simply the
individual RAG cleavage efficiencies.
The Cleavage Efficiency of the Human Immunoglobulin Heavy Chain
VH Elements by the RAG Complex
IMPLICATIONS FOR THE IMMUNE REPERTOIRE*
*
This work was supported in part by National Institutes of
Health grants (to M. R. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The Rita & Edward Polusky Basic Cancer Research Professor.
To whom correspondence should be addressed: Norris Comprehensive Cancer
Ctr., Rm. 5428, University of Southern California, Keck School of
Medicine, 1441 Eastlake Ave., Mail Code 9176, Los Angeles, CA
90089-9176. Tel.: 323-865-0568; Fax: 323-865-3019; E-mail: lieber@usc.edu.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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