mal Tat are in progress. Dr. Peterlin is now using 
genetic and biochemical approaches to isolate, char- 
acterize, and express proteins that interact with the 
Tat activation domain. 
Dr. Peterlin is also Associate Professor of Medi- 
cine and of Microbiology and Immunology at the 
University of California, San Francisco. 
Books and Chapters of Books 
Peterlin, B.M. 1991. Transcriptional regulation of 
HIV. In Genetic Structure and Regulation of HIV 
(Haseltine, W.A., and Wong- Staal, F., Eds.). New 
York: Raven, pp 237-250. 
Articles 
Alonso, A., Derse, D., and Peterlin, B.M. 1992. Hu- 
man chromosome 1 2 is required for optimal in- 
teractions between Tat and TAR of human immu- 
nodeficiency virus type 1 in rodent cells. / Virol 
66:4617-4621. 
Carroll, R., Peterlin, B.M., and Derse, D. 1992. In- 
hibition of human immunodeficiency virus type 1 
Tat activity by coexpression of heterologous 
trans activators. / K/ro/ 66:2000-2007. 
Derse, D., Carvalho, M., Carroll, R., and Peterlin, 
B.M. 1991. A minimal lentivirus Tat. / Virol 
65:7012-7015. 
Modesti, N., Garcia, J., Debouck, C, Peterlin, B.M., 
and Gaynor, R. 1 99 1 . Trans-dominant Tat mutants 
with alterations in the basic domain inhibit HIV-1 
gene expression. New Biol 3:759-768. 
Peterlin, B.M. 1991. Transcriptional regulation of 
HLA-DRA gene. Res Immunol 142:393-399. 
Voliva, C.F., Aronheim, A., Walker, M.D., and Pe- 
terlin, B.M. 1992. B-cell factor 1 is required for 
optimal expression of the DRA promoter in B 
cells. Mol Cell Biol 12:2383-2390. 
GENERATING A REPERTOIRE OF ANTIGEN-SPECIFIC RECEPTORS 
DURING DEVELOPMENT OF THE IMMUNE SYSTEM 
David G. Schatz, Ph.D., Assistant Investigator 
Recognition of infectious agents and other non- 
self antigens by the immune system depends on anti- 
gen receptor molecules (immunoglobulins and T 
cell receptors) expressed on the surface of B and T 
lymphocytes. Each immunoglobulin and T cell re- 
ceptor molecule is highly specific for a given anti- 
gen, so the immune system requires a wide array of 
different receptors to cope with the diversity of po- 
tential antigens in the environment. The myriad dif- 
ferent genes needed to encode these receptors are 
assembled from component gene segments by a site- 
specific recombination process known as V(D)J re- 
combination (so named for the V [variable], D [di- 
versity], and J [joining] gene segments used in the 
reaction). V(D)J recombination, unique and essen- 
tial to the development of B and T lymphocytes, is 
the only truly site-specific recombination process 
known in vertebrates. Dr. Schatz's laboratory is inter- 
ested in answering two fundamental questions con- 
cerning V(D)J recombination: What is the biochemi- 
cal mechanism of the reaction? What molecular 
mechanisms regulate the reaction during lymphoid 
development? 
This recombination reaction has been intensively 
studied since its discovery in 1976, yet little has 
been learned about the enzymatic machinery (re- 
combinase) that carries it out. Particularly frustrat- 
ing had been the inability to identify the gene or 
genes encoding the V(D)J recombinase, despite a 
detailed understanding of the substrates and prod- 
ucts of the reaction. Dr. Schatz, while working in Dr. 
David Baltimore's laboratory, developed a novel, ge- 
netic approach for the identification and isolation of 
such genes. It combined a sensitive assay for V(D)J 
recombinase activity with a standard gene transfer 
technique (genomic transfection) . This approach 
allowed Drs. Schatz, Marjorie Oettinger, and Balti- 
more to identify a genomic locus that could activate 
the V(D)J recombinase when transferred into non- 
lymphoid cells, and subsequently to demonstrate 
that two genes within that locus were necessary and 
sufficient for this activity. These two recombina- 
tion-activating genes (RAG-1 and RAG-2) have be- 
come the prime candidates for the genes that en- 
code the critical, lymphoid-specific components of 
the V(D)J recombinase. 
In their further characterization of RAG-1 and 
RAG-2, Dr. Schatz and his colleagues demonstrated 
that the two genes are coexpressed only in develop- 
ing lymphocytes — in exactly those cells that are as- 
sembling immunoglobulin and T cell receptor 
genes. In collaboration with Dr. Jerold Chun, how- 
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