Presence of HLA-DR molecules and HLA-DRB1 mRNA in circulating CD4+ T cells

The human major histocompatibility complex class II (MHCII) isotype HLA-DR is currently used as an activation marker for T cells. However, whether an endogenous protein expression or a molecular acquisition accounts for the presence of HLA-DR on T cells remains undetermined and still controversial. In order to further characterize this phenomenon, we compared several aspects of the presence of the HLA-DR protein to the presence of associated mRNA (HLA-DRB1), focusing on human T cells from peripheral blood of healthy individuals. Using a flow cytometric approach, we determined that the HLA-DR observed on CD4+ T cells was almost exclusively cell surface-associated, while for autologous CD19+ B cells, the protein could be located in the plasma membrane as well as in the cytoplasm. Moreover, negligible expression levels of HLA-DRB1 were found in CD4+ T cells, using an HLA-DRB1 allele-specific qPCR assay. Finally, the presence of HLA-DR was not confined to activated CD4+ and CD8+ T cells, as evaluated by the co-expression of CD25. The functional role of the HLA-DR molecule on T cells remains enigmatic, however, this study presents evidence of fundamental differences for the presence of HLA-DR on T cells from HLA-DR in the context of antigen-presenting cells, which is a well-known phenomenon. Although an inducible endogenous protein expression cannot be excluded for the T cells, our findings suggest that a re-evaluation of the HLA-DR as a T cells activation marker is warranted. This article is protected by copyright. All rights reserved.