title: Presence of HLA-DR Molecules and HLA-DRB1 mRNA in Circulating CD4(+) T Cells.
abstract: 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-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.
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark. anlor@rn.dk.
authors.forename: A L S
authors.identifier: http://orcid.org/0000-0003-1840-0259
authors.initials: AL
authors.lastname: Revenfeld
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: R
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: L H
authors.initials: LH
authors.lastname: Pugholm
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: M M
authors.initials: MM
authors.lastname: Jørgensen
authors.affiliation: Laboratory for Medical Mass Spectrometry, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Stensballe
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Varming
mesh_terms: D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; D059811:HLA-DRB1 Chains; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger