Presence of HLA ‐ DR Molecules and HLA ‐ DRB 1 mRNA in Circulating CD 4 + T Cells

The human major histocompatibility complex class II 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. To further characterize this phenomenon, we compared several aspects of the presence of the HLA ‐ DR protein to the presence of associated mRNA ( HLA ‐ DRB 1 ), focusing on human T cells from peripheral blood of healthy individuals. Using a flow cytometric approach, we determined that the HLA ‐ DR observed on CD 4 + T cells was almost exclusively cell surface‐associated, while for autologous CD 19 + B cells, the protein could be located in the plasma membrane as well as in the cytoplasm. Moreover, negligible expression levels of HLA ‐ DRB 1 were found in CD 4 + T cells, using an HLA ‐ DRB 1 allele‐specific qPCR assay. Finally, the presence of HLA ‐ DR was not confined to activated CD 4 + and CD 8 + T cells, as evaluated by the co‐expression of CD 25. 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.