Human monoclonal antibody with T‐cell‐like specificity recognizes MHC class I self‐peptide presented by HLA‐DR1 on activated cells

Wölpl, A; Haider, Thomas; Kalbacher, Hubert; Neumeyer, H.; Siemoneit, K.; Goldmann, S. F.; Eiermann, Thomas

doi:10.1111/j.1399-0039.1998.tb03100.x

Cited by 19 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address this, we used a mAb (UL-5A1) that recognizes a distinctive MHC class II:self-peptide complex containing HLA-DRB1*0101 and a peptide derived from HLA-A2 (HLA-A2 103-117 ). 9 Accordingly, this reagent stained B cells of HLA-DRB1*0101 ϩ HLA-A2 ϩ donors but not B cells from donors lacking one of these or both alleles ( Figure 6A). To see whether ECs express defined self-peptide:MHC class II complexes in vivo, dermal cells from HLA-genotyped, healthy volunteers were subjected to 5-color flow cytometry.…”

Section: Resting Microvascular Becs In Vivo Express Cell-surface-bounmentioning

confidence: 96%

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Amatschek

Kriehuber

Bauer

et al. 2007

Blood

127

101

View full text Add to dashboard Cite

The discovery of marker proteins of human blood (BECs) and lymphatic endothelial cells (LECs) has allowed researchers to isolate these cells. So far, efforts to unravel their transcriptional and functional programs made use of cultured cells only. Hence, it is unknown to which extent previously identified LEC-and BEC-specific programs are representative of the in vivo situation. Here, we define the human BEC-and LEC-specific in vivo transcriptomes by comparative genomewide expression profiling of freshly isolated cutaneous EC subsets and of non-EC skin cells (fibroblasts, mast cells, dendritic cells, epithelial cells). Interestingly, the expression of most of the newly identified EC subset-discriminating genes depends strictly on the in vivo tissue environment as revealed by comparative analyses of freshly isolated and cultured EC subsets. The identified environment-dependent, EC subsetrestricted gene expression regulates lineage fidelity, fluid exchange, and MHC class II-dependent antigen presentation.As an example for a BEC-restricted in vivo function, we show that non-activated BECs in situ, but not in vitro, assemble and display MHC class II protein complexes loaded with self-peptides. Thus, our data demonstrate the key importance of using precisely defined native IntroductionThe microvasculature is actively involved in metabolism and immune cell trafficking. Although the supply with oxygen and nutrients as well as the attraction of leukocytes is accomplished by blood vessels, the removal of extracellular fluid from the tissues and the guidance of immune cells to lymph nodes are carried out by lymphatic vessels. At the molecular level, these different functional capabilities are likely encoded by the transcriptional repertoires of blood vessel endothelial cells (BECs) and lymphatic ECs (LECs). Recently, the discovery of the LEC-specific marker proteins podoplanin (PDPN) and LYVE-1 allowed researchers to isolate and propagate BECs and LECs in vitro. 1,2 Accordingly, several techniques, including genomewide expression profiling coupled to bioinformatic approaches, have been used to identify the spectrum of genes that are expressed in cultured LECs and BECs. [3][4][5][6] However, probably as a result of technical limitations, genomewide analyses were not performed on freshly isolated ECs. Thus, it is possible that ECs, in their tissue-resident state, have a transcriptional and, thus, functional repertoire that differs from that of cultured ECs. In fact, the specialized ECs of high endothelial venules rapidly lose EC subset-defining antigen expression and morphology when these cells were placed in culture. 7 This supports that active signal exchange between ECs and the local tissue environment can also be of critical importance for the maintenance of differentiation and function of LECs and BECs.To address whether and, if so, to which extent tissue-resident LECs or BECs resemble their cultured counterparts, we established for the first time the complete transcriptomes of freshly isolated cutaneous LECs, BECs, a...

show abstract

Section: Resting Microvascular Becs In Vivo Express Cell-surface-bounmentioning

confidence: 96%

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Amatschek

Kriehuber

Bauer

et al. 2007

Blood

127

101

View full text Add to dashboard Cite

show abstract

“…The rather small difference in peptide loading by iDCs and B cells may be explained by the fact that iDCs, but less so B cells, express empty and thus peptide-receptive MHC class II dimers (21). B cells also formed 1.8-fold more pMHC complexes than iDCs when we pulsed a different peptide (HLA-A2 103-117 ) onto HLA-DR1-positive APCs and detected HLA-DR1-HLA-A2 103-117 complexes by a specific mAb (17) and cytofluorometry (data not shown). Prevalence of HLA-DR1-HLA-A2 103-117 display by B cells over iDCs was also seen in HLA-DR1-positive APCs that express HLA-A2 and load HLA-A2 103-117 via the endogenous pathway of pMHC formation (data not shown).…”

Section: Pmhc Complexes On Dcs Are Uniquely Efficient In Down-modulatmentioning

confidence: 98%

Dendritic Cells Sensitize TCRs through Self-MHC-Mediated Src Family Kinase Activation

Meraner

Hořejšı́

Wölpl

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

It is unclear whether peptide-MHC class II (pMHC) complexes on distinct types of APCs differ in their capacity to trigger TCRs. In this study, we show that individual cognate pMHC complexes displayed by dendritic cells (DCs), as compared with nonprofessional APCs, are far better in productively triggering Ag-specific TCRs independently of conventional costimulation. As we further show, this is accomplished by the unique ability of DCs to robustly activate the Src family kinases (SFKs) Lck and Fyn in T cells even in the absence of cognate peptide. Instead, this form of SFK activation depends on interactions of DC-displayed MHC with TCRs of appropriate restriction, suggesting a central role of self-pMHC recognition. DC-mediated SFK activation leads to “TCR licensing,” a process that dramatically increases sensitivity and magnitude of the TCR response to cognate pMHC. Thus, TCR licensing, besides costimulation, is a main mechanism of DCs to present Ag effectively.

show abstract

“…All beads with normalized median fluorescence intensity value >2,500 (>1,500 when antibodies were donorspecific) were considered positive. The cut-off point was established based on the results with the human monoclonal antibody UL5A1 [21].…”

Section: Hla Antibodiesmentioning

confidence: 99%

Elevated serum levels of B-cell activating factor in pediatric renal transplant patients

et al. 2012

View full text Add to dashboard Cite

Human monoclonal antibody with T‐cell‐like specificity recognizes MHC class I self‐peptide presented by HLA‐DR1 on activated cells

Cited by 19 publications

References 40 publications

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Blood and lymphatic endothelial cell-specific differentiation programs are stringently controlled by the tissue environment

Dendritic Cells Sensitize TCRs through Self-MHC-Mediated Src Family Kinase Activation

Elevated serum levels of B-cell activating factor in pediatric renal transplant patients

Contact Info

Product

Resources

About