lial cells expressing class I and class II MHC mole- 
cules are responsible for this selection. Heretofore, 
however, there has been no tumor model for posi- 
tive selection. In collaboration with Dr. Barbara 
Knowles (Wistar Institute), Dr. Bevan's laboratory 
has identified a line of simian virus 40 (SV40)- 
transformed thymic epithelial cells that, when in- 
jected intrathymically, mediates the selection of cy- 
totoxic T cells. Because the antigen-processing and 
presentation system of this cell appears to be quite 
conventional, i.e., like that of every other cell in the 
body, the result implies that the peptide-MHC com- 
plexes that mediate positive selection do not differ 
from those that mediate negative selection. It has 
been suggested that the positively selecting MHC 
molecules express a different range of peptides 
from normal cells, but this no longer seems likely. 
The tumor cell line grows well in vitro and will 
be a useful tool to study other facets of positive se- 
lection. For example, one can regulate the levels of 
MHC expressed by this cell and add, or possibly take 
away, certain other accessory molecules to study 
their influence on positive selection. 
A grant from the National Institute of Allergy and 
Infectious Diseases provided support for the project 
described above. 
Dr. Bevan is also Professor of Immunology at 
the University of Washington, Seattle. 
Articles 
Attaya, M., Jameson, S., Martinez, C.K., Hermel, E., 
Aldrich, C, Forman, J., Fischer Lindahl, K., Be- 
van, M.J., and Monaco, J.J. 1992. Ham- 2 corrects 
the class I antigen-processing defect in RMA-S 
cells. Nature 355:647-649. 
Grandea, A.G., III, and Bevan, M.J. 1992. Single- 
residue changes in class I major histocompatibil- 
ity complex molecules stimulate responses to self 
peptides. Proc Natl Acad Sci USA 89:2794- 
2798. 
Harty, J.T., and Bevan, M.J. 1992. CD8+ T cells 
specific for a single nonamer epitope of Listeria 
monocytogenes are protective in vivo, f Exp Med 
175:1531-1538. 
Hosken, N.A., and Bevan, M.J. 1992. An endoge- 
nous antigenic peptide bypasses the class I anti- 
gen presentation defect in RMA-S. / Exp Med 
175:719-729. 
Pamer, E.G., Harty, J.T., and Bevan, M.J. 1991. 
Precise prediction of a dominant class I MHC- 
restricted epitope of Listeria monocytogenes. 
Nature 353:852-855. 
Pamer, E.G., Wang, C.-R., Flaherty, L., Fischer Lin- 
dahl, K., and Bevan, M.J. 1992. H-2M3 presents 
a Listeria monocytogenes peptide to cytotoxic T 
lymphocytes. Ce// 70:215-223- 
STRUCTURAL STUDIES OF CELL SURFACE MOLECULES INVOLVED IN RECOGNITION 
BY THE IMMUNE AND NERVOUS SYSTEMS 
Pamela J. Bjorkman, Ph.D., Assistant Investigator 
Dr. Bjorkman and her colleagues are interested in 
the structure and function of molecules involved in 
cell surface recognition, particularly those that me- 
diate the immune response. Their approach is three- 
fold, combining x-ray crystallography to determine 
three-dimensional structures, molecular biological 
techniques to produce and modify proteins for crys- 
tallization, and biochemistry to study the proteins 
made. 
T Cell Recognition 
T cells have a complicated recognition system 
that includes a membrane-bound receptor (the T 
cell receptor, or TCR), the multisubunit CD3 mole- 
cule, and the accessory or co-receptor molecule 
CD4 or CDS. A fundamental difference between rec- 
ognition by T cells and by antibodies is that antibod- 
ies bind to soluble antigens, whereas TCRs recog- 
nize a fragmented form of the antigen (derived 
through intracellular processing) bound to a mol- 
ecule of the major histocompatibility complex 
(MHC) . MHC molecules bind peptides derived from 
self and foreign proteins during synthesis and transit 
to the cell surface. In this work the laboratory seeks 
a molecular understanding of MHC-peptide inter- 
actions and TCR recognition of MHC-peptide 
complexes. 
Crystallization of a TCR and its MHC-peptide 
ligand. In collaboration with Dr. Mark Davis 
(HHMI, Stanford University), a project has been ini- 
tiated to crystallize soluble forms of a TCR and the 
MHC-peptide complex it recognizes. Crystals of 
2B4, a well-characterized TCR with specificity for 
the class II molecule IE** complexed with a peptide 
of pigeon cytochrome c, have been obtained, as well 
as crystals of the IE''-cytochrome c peptide com- 
IMMUNOLOGY 309 
