expressing mice of an background, even 
though such mice could produce in vitro alloge- 
neic responses against I-A'^. When T cells from non- 
transgenic and transgenic H-2'' mice were activated 
in vitro by I-A'* allogeneic stimulator cells and 
transferred to transgenic mice, an intense, destruc- 
tive lymphocytic infiltrate specific for exocrine pan- 
creas developed. These findings suggest that aber- 
rant class II MHC expression alone does not trigger 
autoimmune reactions, nor does it cause clonal de- 
letion of functional autoreactive cells. Rather, the 
unresponsiveness to allogeneic class II MHC may 
result from the inability of exocrine pancreas to ini- 
tiate primary responses by T cells. 
The data obtained from the TCR and MHC trans- 
genic mice strongly suggest that both clonal dele- 
tion and peripheral "anergy" may be operational 
in vivo to explain self-tolerance. 
IV Molecular Genetics of TCR P-Chain Genes. 
To elucidate the basis for the tissue and develop- 
mental stage-specific expression of the TCR P-chain 
genes. Dr. Loh and his colleagues have continued 
to analyze the transcriptional apparatus. Both in 
vivo and in vitro analyses have been used to iden- 
tify a regulatory region of the murine V(3 promoter. 
PUBLICATIONS 
The results of transient transfection assays indicate 
that the dominant transcription-activating element 
within the V38.3 promoter is the palindromic motif 
previously identified as the conserved vp decamer 
(AGTGACATCA). Elimination of this element, by lin- 
ear deletion or specific mutation, reduces 10-fold 
the transcriptional activity from this promoter. DNase 
I footprinting, gel-mobility shift, and methylation 
interference assays confirm that the palindrome 
acts as the binding site of a specific nuclear factor. 
In particular, the vp promoter motif functions in 
vitro as a high-affinity site for a previously charac- 
terized transcription activator, ATF/CREB (activating 
transcription factor/cAMP-responsive element-bind- 
ing protein). A consensus CRE, but not a consensus 
AP-1 site, can substitute for the decamer in vivo. 
These data suggest that ATF/CREB or related pro- 
teins activate Vp transcription. Since the decamer 
motif has been found in other T cell relevant genes, 
such as terminal deoxynucleotidyl transferase and 
CDS, further work may elucidate the mechanism of 
coordinate gene expression in T cells. 
Dr. Loh is also Associate Professor of Medicine, 
Microbiology and Immunology, and Genetics at 
Washington University School of Medicine and As- 
sistant Physician at Barnes Hospital, St. Louis. 
Articles 
Haqqi, T.M., Banerjee, S., Jones, WL., Anderson, G., Behlke, M.A., Loh, D.Y, Luthra, H.S., and David, C.S. 
1989. Identification of T-cell receptor Vp deletion mutant mouse strain AU/ssJ (H-2'5) which is resistant to 
collagen-induced arthritis. Immunogenetics 29:180-185. 
Sha, WC, Nelson, C.A. , Newberry R.D. , Kranz, D.M., Russell, J.H., and Loh, D.Y 1988. Selective expression of 
an antigen receptor on CD8-bearing T lymphocytes in transgenic mice. Nature 335:271-274 . 
Sha, WC, Nelson, C.A. , Newberry, R.D. , Kranz, D.M., Russell, J.H., and Loh, D.Y 1988. Positive and negative 
selection of an antigen receptor on T cells in transgenic mice. Nature 336:73-76. 
TiUinghast, J.P, Russell, J.H., Fields, L.E., and Loh, D.Y 1989. Protein kinase C regulation of terminal 
deoxynucleotidyl transferase. J Immunol 143:2378-2383. 
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