Generating a Repertoire of Antigen-Specific Receptors 
Thompson (HHMI, University of Michigan) and 
Larry Turka suggest that signals transduced 
through membrane-bound TCR molecules may 
play a role in mediating the termination of 
V(D)J recombinase expression during T cell 
development. 
V(D)J recombination is also regulated at the 
ievel of the availability, or accessibility, of the 
gene segments to the V(D)J recombinase . Accessi- 
bility in turn appears to be mediated by, or paral- 
leled by, transcription of the unrearranged 
("germline") gene segments. Analysis of germ- 
line transcription during B cell development has 
yielded important insights into the relationship 
between transcription and accessibility but has 
left unaddressed important questions concerning 
T cell development. We are interested both in 
how a stem cell (a cell with the potential to de- 
velop into multiple cell types) becomes commit- 
ted to the T cell lineage and how the different 
sublineages of T cells are established. Since the 
regulation of V(D)J recombination is interwoven 
with these developmental decisions, we are ex- 
amining the structure and developmental profile 
of germline TCR gene transcripts. We hope to de- 
termine the sequence of molecular events that 
lead to the assembly of TCR genes and to ask 
whether defects in this process contribute to the 
pathogenesis of immunological disease, particu- 
larly autoimmunity. 
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