M^yrnpnuvyiK uijjertmnanan ana Aciivaiiun 
interferon-responsive elements. We are examin- 
ing deletion and point mutation analysis of these 
promoters, using transient and stable transfec- 
tants. The segments of DNA that control differ- 
ences in tissue-specific expression are being 
defined in transfected cell lines, and the DNA- 
binding proteins that control the expression of 
these genes are also under study. 
One of the most fundamental interactions in 
the immune system is that of the TCR with MHC 
plus ligand. We have produced large amounts of 
soluble MHC class I- and class Il-restricted TCRs 
to study the molecular interactions. We have 
been able to inhibit the functional activity of T 
cell clones by the addition of TCR molecules to 
block the interaction of T cells and antigen-pre- 
senting cells. 
Regulation of tissue-specific expression of 
exons is a major form of gene regulation. We have 
molecularly cloned the protein that binds the 
polypyrimidine regions at 3' splice junctions. 
This protein may be one of the more significant 
factors that determine the splicing pattern of a 
given gene. The region in the protein that con- 
tacts RNA contains a novel RNA recognition motif 
(RRM) . We are characterizing this RRM, as well as 
modifying the expression of the gene product in 
T cell clones, to determine whether this protein 
in a cell can alter the splicing pattern of genes. 
A primary response generates antibodies and 
immunologic memory. We are studying the mo- 
lecular mechanisms that generate B cell memory 
and the relationship of somatic mutation to that 
process. Studies of a primary immune response 
have indicated several new aspects of early 
events. The early response has an oligoclonal 
structure, and hypermutation begins earlier than 
previously recognized. The properties of newly 
acquired somatic mutations indicate the exis- 
tence of a difi'erentiation pathway in which muta- 
tion is inactive. Once the memory lineages are 
generated, they continue to mutate. The second- 
ary immunization triggers a new round of prolifer- 
ation and mutation. 
56 
