T cells. In collaboration with Dr. Stefan Kaufmann's 
laboratory (University of Ulm) , they showed that the 
TCR |8 mutant mice are as resistant to Listeria mono- 
cytogenes infection as the wild-type mice. In vivo 
treatment of the TCR mutant mice with anti-75 
TCR antibody exacerbated L. monocytogenes by 
nearly 100-fold, suggesting a role for yb T cells in 
resistance to this infection. A similar finding was 
made for vaccinated TCR (8 mutant mice against sec- 
ondary Listeria infection. 
In collaboration with Dr. Ruth Nussenzweig's lab- 
oratory (New York University) , Dr. Tonegawa's labo- 
ratory also showed that mice vaccinated with mouse 
malaria-causing Plasmodium yoelii are partially re- 
sistant to secondary infection with the same para- 
site. A 76 T cell clone isolated from the spleen of the 
infected mice could confer a partial resistance to P. 
yoelii. (This project has been supported in part by 
grants from the National Institutes of Health.) 
Dr. Tonegawa is also Professor of Biology at the 
Massachusetts Institute of Technology and at the 
Center for Cancer Research. 
Articles 
Abeliovich, A., Gerber, D., Tanaka, O., Katsuki, M., 
Graybiel, A.M., and Tonegawa, S. 1992. On so- 
matic recombination in the central nervous sys- 
tem of transgenic mice. Science 257:404-410. 
Haas, W., and Tonegawa, S. 1992. Development 
and selection of yb T cells. Curr Opin Immunol 
4:147-155. 
Kappes, D.J., and Tonegawa, S. 1991- Surface ex- 
pression of alternative forms of the TCR/CD3 
complex. Proc Natl Acad Sci USA 88:106X9- 
10623. 
Mombaerts, P., lacomini, J., Johnson, R.S., Herrup, 
K., Tonegawa, S., and Papaioannou, V.E. 1992. 
RAG- 1 -deficient mice have no mature B and T 
lymphocytes. Ce// 68:869-877. 
Pereira, P., Zijlstra, M., McMaster, J., Loring, J.M., 
Jaenisch, R., and Tonegawa, S. 1992. Block- 
ade of transgenic yb T cell development in ^2' 
microglobulin deficient mice. EMBO J 11:25- 
31. 
Silva, A.J., Paylor, R., Wehner, J.M., and Tonegawa, 
S. 1992. Impaired spatial learning in a-calcium- 
calmodulin kinase II mutant mice. Science 
257:206-211. 
Silva, A.J., Stevens, C.F., Tonegawa, S., and Wang, 
Y. 1992. Deficient hippocampal long-term po- 
tentiation in a-calcium-calmodulin kinase II mu- 
tant mice. Science 257:201-206. 
CELL SURFACE MOLECULES AND MOLECULAR EVENTS INVOLVED IN HUMAN 
T CELL ACTIVATION 
Arthur Weiss, M.D., Ph.D., Associate Investigator 
A T lymphocyte response to a specific antigen is 
initiated during a complex intercellular interaction 
with an antigen-presenting cell (APC), and central 
to this response is the T cell antigen receptor (TCR) . 
The TCR has two functions: to recognize the anti- 
genic peptide bound to a molecule of the major his- 
tocompatibility complex, and to conven this recog- 
nition event into a transmembrane signal initiating 
cellular differentiation and proliferation. Although 
the specificity of the response suggests that its initia- 
tion pivots on the interaction of the TCR with anti- 
gen, other molecules expressed on the plasma 
membrane are now seen to play important roles in 
regulating the activation of the T cell. In addition to 
the TCR, Dr. Weiss's laboratory has focused on the 
function of CD45 and CD28. 
TCR Structure and Function 
The TCR is an extraordinarily complex structure 
composed of at least eight chains, the products of 
six genes. The Ti subunit, a heterodimer of a and 0 
chains derived from immunoglobulin (Ig)-like 
genes, is responsible for antigen recognition. Non- 
covalently associated with Ti in an obligatory man- 
ner are the invariant CD3 and f subunits. The CD3 
subunit comprises three homologous chains, 7, 5, 
and two copies oft. The f subunit is a homodimer or 
heterodimer of f and an alternatively spliced form of 
the r; chain, or the 7 chain of the IgE Fc receptor. 
The CD3 and f subunits couple the Ti subunit to 
intracellular signal transduction components. 
The complex structure of the TCR has impeded a 
simple structure-function analysis. However, stud- 
IMMUNOLOGY 365 
