microorganisms is similar, but the proteins are 
much different in structure. 
A well-defined group of superantigens are the ex- 
otoxins produced by streptococcal and staphylococ- 
cal bacteria that cause food poisoning and toxic 
shock syndrome. These toxins are secreted globular 
proteins. Dr. Kappler's group has studied one of 
them in detail, staphylococcal enterotoxin B (SEB). 
They identified amino acids, especially in the 
amino-terminal region, that controlled the toxin's 
ability to bind to MHC molecules. Other amino 
acids in the same portion of the molecule were 
found to control the interaction with the V|8 portion 
of the T cell receptor. 
Dr. Kappler's group has also studied a set of su- 
perantigens that they found to be encoded by a gene 
(vsag) in the 3'LTR (long terminal repeat) of mouse 
mammary tumor viruses (MTVs). The viruses are 
passed in the milk from mother to pup. The retrovi- 
rus appears to use these superantigens to create a 
large set of activated T cells (and indirectly B cells) 
that the virus can infect while awaiting the matura- 
tion of its ultimate target tissue, the mammary 
gland. The viral superantigens have no sequence ho- 
mology with the bacterial ones, and their structures 
are much different. Through use of biochemical 
techniques and monoclonal antibodies specific for 
the viral superantigens, the proteins were shown to 
be type II integral membrane proteins with the un- 
usual property of an extracellular carboxyl-terminal 
region. An examination of these vsag genes from a 
large set of infectious and integrated proviral MTVs 
revealed an extraordinary heterogeneity in se- 
quence and length of the protein's 20-30 amino 
acids in the carboxyl-terminal region, correlating 
with V/3 specificity. 
An extensive analysis of the site of interaction be- 
tween superantigens and VjS elements of the T cell 
receptor has been performed. Based on the similari- 
ties between T cell receptors and antibodies, these 
results indicate that both bacterial and MTV super- 
antigens interact with Vj8s on a solvent-exposed site 
facing away from the site that interacts with conven- 
tional peptide antigens bound to MHC. Thus the bac- 
terial and viral superantigens seem to be an unusual 
example of convergent evolution in which two pro- 
teins have evolved to have the same function and 
occupy proximate sites, but apparently with very 
little structural homology. (This work has received 
support from the National Institutes of Health.) 
Dr. Kappler is also a member of the Division of 
Basic Immunology of the Department of Medicine 
at the National fewish Center for Immunology 
and Respiratory Medicine, Denver, and Professor 
of Microbiology and Immunology and of Medi- 
cine at the University of Colorado Health Sciences 
Center, Denver. 
Articles 
Choi, Y., Kotzin, B., Lafferty, J., White, J., Pigeon, 
M., Kubo, R., Kappler, J., and Marrack, P. 1991 . 
A method for production of antibodies to human 
T-cell receptor jS-chain variable regions. Proc 
Natl Acad Sci USA 88:8357-8361. 
Choi, Y., Marrack, P., and Kappler, J.W. 1992 
Structural analysis of a mouse mammary tumor 
virus supcvdLntigcn. f Exp Med 175:847-852. 
Finkel, T.H., Kappler, J.W., and Marrack, P.C. 
1992. Immature thymocytes are protected from 
deletion early in ontogeny. Proc Natl Acad Sci 
USA 89:3372-3374. 
Herman, A., Labrecque, N., Thibodeau, J., 
Marrack, P., Kappler, J.W., and Sekaly, R. P. 
1991. Identification of the staphylococcal enter- 
otoxin A superantigen binding site in the /3l do- 
main of the human histocompatibility antigen 
HLA-DR. Proc Natl Acad Sci USA 88:9954-9958. 
Ignatowicz, L., Kappler, J., and Marrack, P. 
1992. The effects of chronic infection with a 
superantigen-producing virus. / Exp Med 175: 
917-923. 
Kappler, J.W., Herman, A., Clements, J., and 
Marrack, P. 1992. Mutations defining functional 
regions of the superantigen staphylococcal entero- 
toxin ^.f Exp Med 175:387-396. 
McCormack, J.E., Wade, T., Morales, H., 
Kappler, J., and Marrack, P. 1991. Analysis of 
class II MHC structure in thymic nurse cells. Cell 
Immunol 138:413-422. 
PuUen, A.M., Choi, Y., Kushnir, E., Kappler, J., 
and Marrack, P. 1992. The open reading frames 
in the 3' long terminal repeats of several mouse 
mammary tumor virus integrants encode V(83- 
specific superantigens. /ii'jcp Merf 175:41-47. 
IMMUNOLOGY 34 1 
