antibodies. This has shown that crosslinking of and 
conformational change in the T cell receptor both 
contribute to T cell activation. Antibodies can cross- 
link the T cell receptor without activating the cell, 
and Fab fragments of activating antibodies do not 
crosslink the T cell receptor and therefore do not 
activate the T cell. The two antibodies given to- 
gether activate the T cell effectively. Furthermore, 
antibodies that bind effectively to the T cell recep- 
tor may or may not induce a physical association of 
the T cell receptor with CD4. 
VI. A New Model for T Cell Repertoire Selection. 
Based on these findings, Dr. Janeway has pro- 
posed that positive selection may involve either 
rare self peptides bound to self MHC molecules or 
MHC molecules alone on thymic epithelium. Bind- 
ing of a T cell receptor to a rare self peptide could 
induce conformational change without crosslink- 
ing. MHC alone, together with co-ligands and co- 
PUBLICATIONS 
receptors, could stabilize crosslinks without gener- 
ating the high-affinity binding leading to conforma- 
tional change that the true ligand for the T cell re- 
ceptor induces. Either state could initiate the signal 
for positive selection. 
These models can be tested by further analysis 
of self peptides on thymic epithelium, using new 
monoclonal antibodies being developed in Dr. 
Janeway's laboratory, and by examining the signals 
transduced in T cells by crosslinking or by confor- 
mational change alone. These studies will form the 
focus of research in Dr. Janeway's laboratory in the 
coming year. In addition, the molecular basis of self 
and non-self MHC recognition, of self peptide bind- 
ing to class II MHC molecules, and of spontaneous 
diabetes mellitus are subjects of active research. 
Dr. Janeway is also Professor of Immunobiology 
at the Yale University School of Medicine and of Bi- 
ology at Yale University. 
Books and Chapters of Books 
Janeway, C.A., Jr. 1988. Immunoschematics: who is guilty of original antigenic sin? In NATO Advanced Study 
Institute — Semiotics of Cellular Communication in the Immune System (Celada, F., Tada, T, Mitchison, 
N.A., and Sercarz, E., Eds.). NATO ASI Series H, vol 23, pp 309-313. 
Janeway, C.A., Jr. 1989. Autoimmunity: a perspective. In The Pancreatic ^Cell: Development, Cell and Molec- 
ular Biology, and Immunopathology . Cold Spring Harbor, NY: Cold Spring Harbor, pp 169-180. 
Reich, E.-E, Sherwin, R.S., Scaringe, D., Murphy, D., and Janeway, C.A., Jr. 1989- Approaches to autoantigens 
in diabetes. In The Pancreatic (3 Cell: Development, Cell and Molecular Biology, and Immunopathology. 
Cold Spring Harbor, NY: Cold Spring Harbor, pp 197-201. 
Articles 
Bonneville, M., Ito, K., Krecko, E.G., Itohara, S., Kappes, D., Ishida, I., Kanagawa, O., Janeway, C.A., Jr., Mur- 
phy, D.B., and Tonegawa, S. 1989. Recognition of a self major histocompatibility complex TL region prod- 
uct by 78 T-cellTeceptorsT^ocA^a^/Ac^^/ 5c/ f/5A 86:5928-5932. 
Bonneville, M., Janeway, C.A., Jr., Ito, K., Haser, W, Ishida, I. , Nakanishi, N., and Tonegawa, S. 1988. Intestinal 
intraepithelial lymphocytes are a distinct set of 78 T cells. Nature 336:479-481. 
Chamberlain, J.W, Nolan, J.A., Conrad, PJ., Vasavada, H.A., Vasavada, H.H., Ganguly, S., Janeway, C.A., Jr. , and 
Weissman, S.M. 1988. Tissue-specific and cell surface expression of human major histocompatibility com- 
plex class I heavy (HLA-B7) and light 02-microglobulin) chain genes in transgenic mice. Proc Natl Acad 
Sci USA 85:7690-7694. 
Gromkowski, S.H., Hepler, K.M., and Janeway, C.A., Jr. 1988. Low doses of interleukin 2 induce bystander 
cell lysis by antigen-specific CD4"'" inflammatory T cell clones in short-term assays. Eur J Immunol 
18:1385-1389. 
Janeway, C.A., Jr. 1988. Do suppressor T cells exist? A reply. Scand J Immunol 27:62 1-623. 
Janeway, C.A., Jr. 1988. Frontiers of the immune system. Nature 333:804-806. 
Janeway, C.A., Jr. 1988. T-cell development. Accessories or coreceptors? A'rt^Mre 335:208-210. 
Continued 
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