CD99 differentially modulate transcriptional regulation of classical MHC class I and CD1a molecules (130.23)

Abstract

Abstract We have previously established that CD99, a ubiquitous surface molecule expressed as two isoforms, could regulate classical MHC class I (class I) expression. Fine tuning of class I during differentiation and activation of professional APC should be crucial event which deserve to be carefully examinated. Surprisingly, we found that expression of CD1a was inversely regulated to class I expression by a mechanism involving CD99. Using the Jurkat cell line, we have demonstrated that Class I and CD1a transcriptions levels are dictated by CD99 long isoform (CD99LF). CD99LF enhances Class I transcription and therefore its expression, while down regulating CD1a. We also showed that this regulation is counteracted in the presence of CD99 short form (CD99SF). Therefore, expression of both CD99 isoforms allows expression of class I and non classical MHC CD1a molecules at plasma membrane without requiring β2M modulation. To confirm our results, we used CD14+ monocytes and their derived dendritic cells. Performing qRT-PCR, flow cytometry and CD99 silencing experiments, we have demonstrated that generation of CD1a positive dendritic cells (mDC1) depends on a mechanism involving an expression switch from CD99LF to both CD99 isoforms. We hypothesize that lack of CD99 switches leads to CD1a negative (mDC2) generation. This regulatory mechanism appears to be therefore crucial for mDC1 or mDC2 orientations, which are distinguished by their different capacities to direct Th cell differentiation.