the PI pathway in response to carbachol, indepen- 
dent of the TCR. Moreover, stimulation of HMl 
leads to several parameters of T cell activation, in- 
cluding IL-2 production, IL-2 receptor expression, 
and the expression of the T cell activation antigen 
CD69. Signal transduction events mediated by HMl 
can even synergize with signals delivered through 
other T cell accessory molecules, such as CD28, in 
inducing IL-2 production. Finally, HMl does not ac- 
tivate tyrosine kinases independent of one that is 
linked to the PI pathway. This suggests that the 
TCR induction of the PI pathway is sufficient for the 
activation of T cells. 
The ability of the HMl receptor to activate the PI 
pathway in Jurkat cells suggested that it would be a 
useful probe to analyze the functional competency 
of distal components of the PI signal transduction 
pathway in the J.CaMl-3 mutants. HMl could acti- 
vate the PI pathway in all three of these signal 
transduction mutants. This suggests that the de- 
fects in these cells affect components that are spe- 
cific for the pathway activated by the TCR. 
III. Identification of Ligand-induced TCR-associated 
Proteins. 
In recent studies, two cell surface glycoproteins 
of 34 and 38 kDa have been identified that associ- 
ate with the TCR after it has bound an agonist. Al- 
kylation of the complex of the TCR and gp34 and 
PUBLICATIONS 
gp38 is required to preserve their association. Asso- 
ciation of these two glycoproteins with the TCR is a 
specific response that depends on stimulation of 
the TCR but not other cell surface molecules. The 
functional significance of their association is sug- 
gested by the fact that these proteins do not associ- 
ate with the TCR on the signal transduction mu- 
tants J.CaMl or J.CaM3 but do associate with the 
TCR of J.CaM2, despite its failure to mediate signal 
transduction through the PI pathway. Hence the as- 
sociation of gp34 and gp38 is not a consequence of 
signal transduction. Further characterization of 
gp34 and gp38 on normal T cells as well as on 
these mutants will help elucidate their role in TCR- 
mediated signal transduction. 
The activation of T cells by antigen is a complex 
process that is initiated during a complex cell-cell 
interaction. These investigations are an attempt to 
define the role of one of the molecules, the TCR, 
primarily regulating these events. Such studies may 
not only help define the role of the TCR in T cell 
activation but may paint a broader picture of how 
cell surface receptors function in mediating trans- 
membrane signaling events and in regulating cell 
interactions. 
Dr. Weiss is also Associate Professor of Medicine 
and of Microbiology and Immunology at the Uni- 
versity of California at San Francisco. 
Books and Chapters of Books 
Goldsmith, M.A., Bockenstedt, L.K., Dazin, P., and Weiss, A. 1988. Use of somatic cell mutants to study the sig- 
nal transduction function of the T cell antigen receptor. In Second International Conference of Lympho- 
cyte Activation and Immune Regulation. New York: Plenum, pp 195-211. 
Goldsmith, M.A., and Weiss, A. 1988. Function of the antigen receptor in T cell activation. In Biology of 
Growth Factors: Molecular Biology, Oncogenes, Signal Transduction, and Clinical Implications (Kudlow, 
J.E., MacLennon, D.H., Bernstein, A., and Gotlieb, A., Eds.). New York: Plenum, pp 195-211. 
Imboden, J.B., and Weiss, A. 1988. Regulation of interleukin-2 production by the T cell antigen receptor. In 
Interleukin 2 (Smith, K.A., Ed.). San Diego, CA: Academic, pp 85-98. 
Weiss, A. 1988. The biology of the T lymphocytes. In Textbook of Rheumatology (Kelley WN., Harris, E.D., 
Ruddy S., and Sledge, C.B., Eds.). Philadelphia, PA: Saunders, ed 3, pp 148-168. 
Articles 
Bockenstedt, L.K., Goldsmith, M.A., Dustin, M., Olive, D., Springer, T.A., and Weiss, A. 1988. The CD2 ligand 
LFA-3 activates T cells but depends on the expression and function of the antigen receptor. / Immunol 
141:1904-1911. 
Goldsmith, M.A., Dazin, PR, and Weiss, A. 1988. At least two non-antigen-binding molecules are required for 
signal transduction by the T-cell antigen receptor. Proc Natl Acad Sci USA 85:8613-8617. 
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