degradation. Dr. Desiderio and his colleagues now 
wish to test this idea and to determine whether their 
observation represents a specific example of a more 
general phenomenon. 
Recognition of the recombination signal se- 
quences of antigen receptor genes. Assembly of an- 
tigen receptor genes is mediated by conserved hep- 
tamer and nonamer DNA sequence elements that lie 
at the sites of recombination. The laboratory has pu- 
rified a specific DNA-binding protein, NBP, whose 
binding site coincides with the nonamer recombina- 
tion signal, suggesting that it is a part of the recombi- 
national machinery. By differential screening of a 
cDNA expression library with wild-type and mutant 
nonamer oligonucleotide probes, the laboratory 
isolated a cDNA clone whose polypeptide product 
binds DNA fragments containing the nonamer re- 
combinational signal. The function of this polypep- 
tide and its relationship to NBP are now under study. 
(The project described in this section is supported 
by a grant from the National Institutes of Health.) 
Genetic Basis of Molecular Mimicry 
by Antibody Molecules 
A long-standing hypothesis is that the structures of 
some antigens may be mimicked by a subset of anti- 
idiotypic antibodies. Dr. Desiderio and his collabo- 
rators Dr. L. Mario Amzel (Department of Biophys- 
ics, Johns Hopkins University School of Medicine) 
and Dr. Pierre M. Ronco (INSERM, Hopital Tenon, 
Paris) have tested this idea by examining an anti- 
idiotypic antibody series. An angiotensin Il-reactive 
antibody (Abl) and an anti-anti-idiorypic antibody 
(Ab3) are related by an anti-idiotypic antibody 
(Ab2-;8) and were found to have identical antigen- 
binding properties. The sequences of the variable 
regions of Ab3 and of Abl were nearly identical, 
even though the Abl was raised against a peptide 
and the Ab3 against a globular protein. Strikingly, 
amino acid residues that make critical contacts with 
antigen in the crystal structure of the Ab 3 -antigen 
complex are highly conserved in Abl, indicating 
that the epitopes of the Ab2-|8 recognized by Ab3 do 
indeed resemble the bound structure of the antigen. 
Signal Transduction 
in Lymphocyte Activation 
Activation of lymphocytes by antigen and lym- 
phokines is likely mediated by protein-tyrosine 
phosphorylation, but the tyrosine kinases involved 
are largely undefined and their functions poorly un- 
derstood. The answers to such questions remain a 
major goal of Dr. Desiderio's laboratory. 
The B lymphoid-specific protein-tyrosine ki- 
nase, Blk. Dr. Desiderio and his colleagues have 
identified a new member of the src family, blk, 
which is expressed specifically in B lymphoid cells 
and encodes a 55-kDa protein-tyrosine kinase, Blk. 
During B cell ontogeny, blk expression is closely 
correlated with expression of two genes, mb-1 and 
B29, which encode the accessory chains of the B 
cell antigen-receptor (sig) complex, suggesting that 
Blk functions in sig-mediated signaling. Preliminary 
experiments suggest a specific physical association 
between Blk and the product of B29, and the struc- 
tural basis for this association is now under study. 
In a separate approach to Blk function, the Desi- 
derio group is constructing lines of transgenic mice 
that express constitutively active or inactive Blk ki- 
nases in B lymphoid cells. If Blk transduces slg- 
mediated signals, the resulting mice may exhibit 
specific defects in B cell development or responsive- 
ness to antigen. 
In addition to Blk, several other Src family ki- 
nases, including Lyn and Fyn, are expressed in B 
cells. All Src kinases, and some other molecules, 
contain a domain (Src-homology region 2, or SH2) 
that binds phosphotyrosine-containing polypep- 
tides. The group has employed affinity chromato- 
graphic methods to identify phosphoproteins whose 
phosphorylation state changes upon B cell activa- 
tion and that bind to specific SH2 subsets. 
Upon terminal differentiation of B cells to plasma 
cells, transcription of blk ceases. A DNA fragment 
containing 451 bp of blk's 5' flank was found suffi- 
cient to support developmental stage-specific ex- 
pression of a heterologous gene in B lymphoid cells. 
By electrophoretic mobility shift assays, two sites 
within this region were found to bind protein (s) 
whose activity is correlated positively with blk ex- 
pression. Studies to determine the functional signifi- 
cance of these interactions and to identify the pro- 
teins that bind these sites are under way. (The 
studies described in this paragraph are supported by 
a grant from the National Institutes of Health.) 
The T lymphoid-specific protein-tyrosine ki- 
nase Itk. Dr. Desiderio and his colleagues have iso- 
lated another novel lymphoid-specific tyrosine ki- 
nase gene, itk (IL-2 [interleukin-2]-inducible T cell 
kinase) . Conceptual translation of the itk sequence 
predicts a 72-kDa tyrosine kinase of unusual struc- 
ture: while it is related to members of the Src family, 
it lacks the amino-terminal myristoylation consen- 
sus sequence and the regulatory, carboxyl-terminal 
tyrosine residue characteristic of Src kinases. Anti- 
bodies elicited by Itk-specific peptides detect a 72- 
kDa phosphoprotein in thymus and cultured T cells. 
As predicted, this protein is associated with protein- 
tyrosine kinase activity. 
Expression of itk is restricted to the T cell lineage, 
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