Differential analysis of CD4+ Th memory clones with identical T-cell receptor (TCR)-alphabeta rearrangement (non-transgenic), but distinct lymphokine phenotype, reveals diverse and novel gene expression

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Abstract
This study describes a subtractive hybridization analysis to identify differences in gene expression between sibling Th memory clones, elicited by virus infection and expressing identical T-cell receptor (TCR)-alphabeta rearrangements but distinct lymphokine phenotype: clone Bpp9 secretes interleukin (IL)-4, IL-5 and IL-10; clone Bpp19 secretes interferon (IFN)-gamma, low levels of IL-4, and IL-5 on TCR ligation. cDNA sequencing of difference products (DP) identified both novel and known regulatory (DNA: RNA-binding) or signalling proteins (kinases: phosphatases). Of the 10 novel genes identified, three were putative membrane proteins, one a predicted nuclear protein containing a PEST sequence motif, one a predicted transporter fragment and one contained a zinc-finger motif. One of the membrane proteins was found only in RNA from the activated IFN-gamma-producing clone, i.e. not in other tissues. In addition, a high frequency of granzyme A, B, C and G transcripts (for clone Bpp9) or transcripts for CD94 and NKG2A (for clone Bpp19) were expressed differentially, together with transcripts that mapped to, so far, unassigned regions of the mouse genome that may be further novel genes. The transcriptional profiles presented here may therefore include candidate regulators of Th diversity and effector function.