Although recombination is mediated through a common recombinase and conserved recombination signals that flank the gene segments, the process is highly regulated in vivo. Finally, only one of the two alleles is functionally recombined and expressed, a process referred to as allelic exclusion. Evidence suggests that the control is through modulating chromatin structures of gene segments and therefore their accessibility to the common recombinase. We have identified cis-regulatory elements that control TCRb gene rearrangement. We are currently investigating the molecular determinants of accessibility and the role of specific trans-factors in this process.
Immunological memory is a central feature of adaptive immunity and is the basis of vaccination.
However, little is known about the differentiation, reactivation, and function of memory T and B cells because of a lack of identifiable markers and their low abundance. We have been developing markers for identifying memory T and B cells and generating large numbers of memory cells for biochemical and functional analyses. One approach we are developing for marking memory T and B cells is to transgenically express an exogenous marker gene when T and B cells are activated by antigen. The second approach we have used to follow memory T cells is to adoptively transfer T cells expressing a transgenic TCR which can be specifically identified by a clonotypic antibody. By the second approach, we have been able to follow T cell immune response to specific antigenic peptide and the resulting memory T cells in vivo.