cancer (human T cell leukemia virus type I, HTLV-I) 
and AIDS (human immunodeficiency virus type 1, 
HIV-1) and the pathological interplay of these vi- 
ruses v^ith immune cells. 
Assistant Investigator B. Matija Peterlin, M.D. 
(University of California at San Francisco) studies 
the copying of genes that are important for normal 
host defense mechanisms. Steps leading to the acti- 
vation and amplification of spread of the virus that 
causes AIDS (HIV-1) also are investigated. Biochem- 
ical and genetic techniques are used to isolate, 
clone, characterize, and express genes that are im- 
portant in these regulatory processes. These stud- 
ies should lead to the identification of the genetic 
factor that is missing in the bare lymphocyte syn- 
drome, a disease vv^here children die at a young age 
of immunodeficiency. They also should increase our 
understanding of mechanisms involved in HIV la- 
tency and progression to active disease. 
In the past year Assistant Investigator Dorothy E. 
Lewis, Ph.D. (Baylor College of Medicine) has fo- 
cused on understanding the effects of HIV on CD8^ 
cells in an in vitro model system. The cells are pro- 
ductively infected in this system, but it is unclear 
whether the cells are infected via a CD4^ cell or by 
another mechanism. This laboratory also is examin- 
ing plant phospholipids for their effect on HIV pro- 
duction in vitro. The compounds are effective in 
their interference and relatively nontoxic. Future 
experiments will explore the mechanisms responsi- 
ble for this interference with HIV production. In 
addition, Dr. Lewis has developed a sensitive in situ 
hybridization technique. In her study of more than 
50 HIV-infected individuals she reports that, in 10 
of 25 AIDS patients, more than 30 out of 10,000 
cells were transcriptionally active. Most impor- 
tantly, increased numbers of transcriptionally active 
cells appear to be correlated with the patient's clin- 
ical condition: this would imply that viremia per se 
could account for the pathology of HIV infection. 
The laboratory of Associate Investigator David D. 
Chaplin, M.D., Ph.D. (Washington University) is in- 
vestigating the structure of the human major histo- 
compatibility complex (MHC). Genes within the 
MHC participate in essentially all phases of the im- 
mune response. The new yeast artificial chromo- 
some (YAC) DNA cloning technology is being used 
to determine the relationship of all the genes 
within the MHC. Y\C clones that define more than 
half of the gene complex have been isolated, and 
these will permit a detailed analysis of the structure 
of the complex. Dr. Chaplin also studies the molec- 
ular and cellular biology of interleukin-1, an impor- 
tant immunomodulatory cytokine. His laboratory 
has produced new reagents that should permit bio- 
chemical analysis of this agent in a variety of immu- 
nologic systems. 
The MHC class II molecules play a pivotal role in 
determining both normal and abnormal immune 
responses. The expression of class II genes is regu- 
lated by a series of genetic elements and a series of 
soluble proteins that bind to these elements. The 
cDNAs encoding two such proteins, YB-1 and YB-2, 
have been isolated, characterized, and sequenced 
by Investigator Benjamin D. Schwartz, M.D., Ph.D. 
(Washington University) and his colleagues. YB-1 
mRNA levels have been found to correlate inversely 
with class II mRNA levels, which suggests that YB-1 
may be a negative regulatory protein. YB-2 appears 
to interact with YB-1 to prevent YB-1 from binding 
to the class II promoter region. The binding of anti- 
genic peptides to the class II molecules has been 
studied using photoaffinity probes, and the site of 
the class II promoter molecules labeled by one 
such photoaffinity probe has been identified. This 
site is relatively hydrophobic, is in close proximity 
to the antigen-binding cleft, and is formed by the 
first halves of the second domain of the a- and (3- 
chains. In addition, one region of the influen- 
za hemagglutinin molecule that is important for 
antigen binding and T cell recognition has been 
identified. 
Investigator Robert R. Rich, M.D. (Baylor College 
of Medicine) and his colleagues have studied struc- 
ture-function relationships in three models of 
MHC-mediated antigen recognition by human and 
mouse T cells. Studies of the maternally transmit- 
ted antigen (Mta) in mice suggest that the nuclear 
gene product involved in Mta expression functions 
as a receptor for a formulated hydrophobic peptide 
encoded by a mitochondrial gene. Sequencing of 
human HLA genes associated with an anomalous 
MHC class II molecule has revealed mutations in 
two adjacent codons of the DRB gene that may ac- 
count for the unusual properties of certain DRl 
molecules. Finally, studies of peptide-MHC class II 
interactions have demonstrated that the staphylo- 
coccal enterotoxins, which display several extraor- 
dinary antigenic properties, exhibit a specific, high- 
affmity interaction with class II MHC molecules, 
leading to class Il-dependent, but MHC allotype- 
and isotype-independent, T cell activation. 
The laboratory of Investigator Kirsten Fischer- 
Lindahl, Ph.D. (University of Texas Southwestern 
Medical Center at Dallas) has continued its analysis 
of the Mta transplantation antigen, with the aim of 
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