T cell responses to human platelet antigen–1a involve a unique form of indirect allorecognition

Ahlén, Maria Therese; Husebekk, Anne; Killie, Ida Løken; Skogen, Bjøŕn; Stuge, Tor B.

doi:10.1172/jci.insight.86558

Cited by 12 publications

(8 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Next, CD4 T cells specific for HPA-1a presented in HLA-DRB3*01:01 [clone D8T108, for isolation and expansion see Ref. ( 37 )] were added in a T:DC ratio of 10:1 in the presence of 500 ng/ml LPS (Invivogen, San Diego, CA, USA). After overnight incubation, culture supernatant was harvested, and IFN-γ production was determined using ELISA (Sanquin Reagents, Amsterdam, Netherlands).…”

Section: Methodsmentioning

confidence: 99%

Storage-Induced Platelet Apoptosis Is a Potential Risk Factor for Alloimmunization Upon Platelet Transfusion

et al. 2018

View full text Add to dashboard Cite

Platelet transfusion can elicit alloimmune responses leading to alloantibody formation against donor-specific polymorphic residues, ultimately resulting in platelet transfusion refractoriness. Universal leukoreduction significantly reduced the frequency of alloimmunization after platelet transfusion, thereby showing the importance of white blood cells (WBCs) in inducing this alloresponse. It is, however, unknown if the residual risk for alloimmunization is caused by WBCs remaining after leukoreduction or if alloimmunization can be induced by platelets themselves. This study investigated the capacity of platelets to induce alloimmunization and identified potential product-related risk factors for alloimmunization. First, internalization of allogeneic platelets by dendritic cells (DCs) was demonstrated by confocal microscopy. Second, after internalization, presentation of platelet-derived peptides was shown by mass spectrometry analysis of human leukocytes antigen (HLA)-DR eluted peptides. Third, platelet-loaded DCs induced platelet-specific CD4 T cell responses. Altogether, this indicates a platelet-specific ability to induce alloimmunization. Therefore, factors enhancing platelet internalization may be identified as risk factor for alloimmunization by platelet concentrates. To investigate if storage of platelets is such a risk factor, internalization of stored platelets was compared with fresh platelets and showed enhanced internalization of stored platelets. Storage-induced apoptosis and accompanied phosphatidylserine exposure seemed to be instrumental for this. Indeed, DCs pre-incubated with apoptotic platelets induced the strongest IFN-γ production by CD4 T cells compared with pre-incubation with untreated or activated platelets. In conclusion, this study shows the capacity of platelets to induce platelet-specific alloimmune responses. Furthermore, storage-induced apoptosis of platelets is identified as potential risk factor for alloimmunization after platelet transfusions.

show abstract

Section: Methodsmentioning

confidence: 99%

Storage-Induced Platelet Apoptosis Is a Potential Risk Factor for Alloimmunization Upon Platelet Transfusion

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The DCs were then harvested and washed three times at 400 g for 5 min using PBS supplemented with 10% mixed human antibody-type serum and IgG-depleted transferrin. Subsequently, DCs specific for Sema7a were mixed with the CD4 + T cells from the same donor at a T:DC ratio of 10:1 in the presence of 500 ng/ml LIPOPOLYSACCHARIDE (LPS; Invitrogen, Carlsbad, California, USA), which promotes DC maturation and antigen presentation [34,35]. After incubation for 12 h, the concentrations of IFN-γ in the culture supernatant were measured by sandwich enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's instructions (BD Biosciences).…”

Section: Human Jmh Antigen (Sema7a)-specific T Cell Responsesmentioning

confidence: 99%

Anti-JMH alloantibody in inherited JMH-negative patients leads to immunogenic destruction of JMH-positive RBCs

Zhang

Wei

Chen

et al. 2021

Clinical and Experimental Immunology

View full text Add to dashboard Cite

The clinical significance of the specific anti-John Milton Hagen (JMH) alloantibody in inherited JMH-negative patients remains unclear. During clinical blood transfusion, it is often classified as an anti-JMH autoantibody in acquired JMH-negative patients, which might further lead to the occurrence of haemolysis events. In this study, we found that the proportion of inherited JMH-negative people in the Guangzhou population was 0.41%, based on the study of 243 blood samples by flow cytometry. Gene sequencing analysis revealed two novel variants located in exon 11 (c.1348G>A, p.Ala449Thr) and exon 14 (c.1989G>T, p.Leu663Phe). Specific antigen presentation showed that JMH-positive RBCs (red blood cells) could be internalized by SEMA7A −/− dendritic cells (DCs) and that SEMA7A −/− DCs activated by the semaphorin 7a (Sema7a) protein or JMH-positive erythrocytes further induced activation of CD4 + T cells to secrete interferon (IFN)-γ. Transfusion of JMH-positive RBCs could lead to the production of the specific anti-JMH alloantibody in Sema7a knock-out (KO) C57 mice. After erythrocyte sensitization, complement C3 was specifically fixed, causing the destruction of JMH-positive erythrocytes. The anti-JMH alloantibody caused immunological destruction of JMH-positive erythrocytes and promoted the clearance of JMH-positive RBCs. We should be cautious when making conclusions about the clinical significance of the anti-JMH alloantibody.

show abstract

“…This tends to demonstrate that the outcome is complex and multifocal. Next, extensive studies on FNAIT have revealed that some mothers displaying certain HLA genotypes (such as DRB4*01:01 and foremost DRB3*01:01 [49,50,51,52]) presented with HPA1-derived peptides more efficiently than their negative counterparts. Similar findings have been obtained in red blood cell immunisation [53] and transplanted organ immunisation where certain HLA genotypes (and minor histocompatibility antigens MICA and MICB) associate with strong donor-specific antibodies or DSAs [54].…”

Section: Fine-tuned Mechanisms Of Alloimmunisation: As Yet Unexploredmentioning

confidence: 99%

Immunological Features in the Process of Blood Platelet-Induced Alloimmunisation, with a Focus on Platelet Component Transfusion

2019

View full text Add to dashboard Cite

Alloimmunisation to platelet antigens is not uncommon; a large number of females, having had pregnancies, developed antibodies to Human Leukocyte Antigen (HLA) moieties harboured on their foetuses’ cells (inherited from the father(s)) that may conflict with further pregnancies and transfused Platelet Components occasionally. This is possible since platelets constitutionally express HLA class I molecules (though in copy numbers that consistently differ among individuals). Platelets also express HPA moieties that are variants of naturally expressed adhesion and aggregation molecules; HPA differences between mothers and foetuses and between donors and recipients explain alloimmune conflicts and consequences. Lastly, platelets express ABO blood group antigens, which are rarely immunising, however transfusion mismatches in ABO groups seem to be related to immunisation in other blood and tissue groups. Transfusion also brings residual leukocytes that may also immunise through their copious copy numbers of HLA class I (rarely class II on activated T lymphocytes, B cells, and dendritic cells). In addition, residual red blood cells in platelet concentrates may induce anti-red blood cell allo-antibodies. This short review aims to present the main mechanisms that are commonly reported in alloimmunisation. It also critically endeavours to examine paths to either dampen alloimmunisation occurrences or to prevent them.

show abstract

T cell responses to human platelet antigen–1a involve a unique form of indirect allorecognition

Cited by 12 publications

References 26 publications

Storage-Induced Platelet Apoptosis Is a Potential Risk Factor for Alloimmunization Upon Platelet Transfusion

Storage-Induced Platelet Apoptosis Is a Potential Risk Factor for Alloimmunization Upon Platelet Transfusion

Anti-JMH alloantibody in inherited JMH-negative patients leads to immunogenic destruction of JMH-positive RBCs

Immunological Features in the Process of Blood Platelet-Induced Alloimmunisation, with a Focus on Platelet Component Transfusion

Contact Info

Product

Resources

About