teraction are adhesion molecules, such as CD28 or 
CD2. This would give adhesion molecule-ligand in- 
teractions a major role in "orchestrating" which T 
cells interact with which antigen-presenting cells. 
This has important implications for autoimmunity, 
in that normally T cells would be expected to 
"focus" on appropriate antigen-presenting cells, 
such as B cells or macrophages, and would 
be hindered in surveying most other cells or 
tissues (which would lack the appropriate ligand 
expression) . 
Requirements for T Cell Activation 
and Inactivation 
How T cells become activated and under what cir- 
cumstances they are inactivated in the periphery are 
central issues in their biology. The laboratory has 
developed a procedure whereby primary CD4^ T 
cells are purified from TCR-a^S transgenic lymph 
nodes and stimulated with antigen-MHC complexes, 
either coated on plates or on cells, alone or in com- 
bination with various putative co-stimulator mole- 
cules (or antibodies directed at such molecules) . In 
this way the minimum requirements for T cell acti- 
vation may be determined and possible scenarios for 
inactivation (anergy) investigated. 
In preliminary results, stimulation of either pri- 
mary or secondary T cells through the TCR alone 
does not appear to result in anergy. Stimulation 
through the protein kinase C (PKC) pathway is re- 
quired for interleukin-2 (IL-2) release in the former 
but not the latter cells. 
This last point links T cell memory with models of 
neuronal memory, where PKC activation is also as- 
sociated with the establishment of a learned re- 
sponse. By using "degenerate" PCR (polymerase 
chain reaction) methodology, the laboratory has 
identified a novel PKC isoform (PKC-T), which is 
expressed specifically in T cells, but not B or other 
circulating cells. This molecule may be an impor- 
tant missing link in the control of T cell stimulation 
in ontogeny and in the periphery. (The projects in 
this section have been funded through a grant from 
the National Institutes of Health.) 
Dr. Davis is also Professor of Microbiology and 
Immunology at Stanford University School of 
Medicine. 
Articles 
Hackett, J., Jr., Stebbins, C, Rogerson, B., Davis, 
M.M., and Storb, U. 1992. Analysis of a T cell re- 
ceptor gene as a target of the somatic hypermuta- 
tion mechanism. / £jcp Merf 176:225-231- 
Jorgensen, J.L., Esser, U., Fazekas de St. Groth, B., 
Reay, P.A., and Davis, M.M. 1992. Mapping T- 
cell receptor-peptide contacts by variant peptide 
immunization of single-chain transgenics. Nature 
355:224-230. 
Jorgensen, J. L., Reay, P.A., Ehrich, E.W., and Davis, 
M.M. 1992. Molecular components of T-cell rec- 
ognition. Annu Rev Immunol 10:835-873- 
Matsui, K., Boniface, J.J., Reay, P.A., Schild, H., 
Fazekas de St. Groth, B., and Davis, M.M. 1991- 
Low affinity interaction of peptide-MHC com- 
plexes with T cell receptors. Science 254:1788- 
1791. 
Reay, P.A., Wettstein, D.A., and Davis, M.M. 1992. 
pH dependence and exchange of high and low 
responder peptides binding to a class II MHC mol- 
ecule. EMBO f 1 1 :2829-2839. 
GENETICS, STRUCTURE, AND FUNCTION OF HISTOCOMPATIBILITY ANTIGENS 
KiRSTEN Fischer Levdahl, Ph.D., Investigator 
Dr. Fischer Lindahl's laboratory studies the mouse 
major histocompatibility complex (MHC) and the 
molecules it encodes. Projects have focused on anti- 
gen presentation by two medial MHC class I mole- 
cules, H-2M3 and Qa-1; on evolution and intraspe- 
cies divergence of /32-microglobulin (/32m), a 
component of all MHC class I antigens; and on map- 
ping, cloning, and characterizing genes in the 
mouse MHC's M region and S-D interval. 
H-2M3 
H-2M3 was defined as the MHC class I molecule 
that presents the maternally transmitted antigen 
of mice, which is a mitochondrially encoded, A'^ 
formylated peptide. An amino-terminal formyl 
group is essential for binding of peptides to M3. 
Mitochondrial and prokaryotic proteins share this 
feature, which distinguishes them from proteins syn- 
thesized on cytosolic ribosomes, and it was there- 
fore reasonable to assume that M3 might also pres- 
ent bacterial peptides and play a role in the immune 
response against infection. This has now been con- 
firmed through a collaboration with the labora- 
tory of Dr. Michael Bevan (HHMI, University of 
Washington) . 
Dr. Eric Pamer (University of Washington) has 
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