Identification, immunomodulatory activity, and immunogenicity of the major helper T-cell epitope on the K blood group antigen

Stephen, Jillian; Cairns, Lindsay S.; Pickford, Wendy; Vickers, Mark A.; Urbaniak, S. J.; Barker, Robert N.

doi:10.1182/blood-2012-02-410324

Cited by 32 publications

(50 citation statements)

References 40 publications

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“…RBC antigen presentation has been investigated in a few human studies, and it is now thought that HLA restriction does exist for some RBC antigens, such as Fya [16,72] and potentially Kell [73], but not for others, in particular Rh(D) [59]. Certain HLA types may also be more likely to be associated with a ‘responder' phenotype [74].…”

Section: Recipient Factorsmentioning

confidence: 99%

“…Evidence for past non-RBC exposure priming for subsequent responses to RBC antigens exists in humans [73] and in animals [60]. Peripheral blood mononuclear cells from humans with no detectable anti-KEL alloantibodies were stimulated with overlapping KEL peptides, with evidence of T-cell reactivity present in subjects with no prior RBC exposure [73].…”

Section: Recipient Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

Ryder

Zimring

Hendrickson

2014

Transfus Med Hemother

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Red blood cell (RBC) alloimmunization may occur following transfusion or pregnancy/delivery. Although observational human studies have described the immunogenicity of RBC antigens and the clinical significance of RBC alloantibodies, studies of factors influencing RBC alloimmunization in humans are inherently limited by the large number of independent variables involved. This manuscript reviews data generated in murine models that utilize transgenic donor mice, which express RBC-specific model or authentic human blood group antigens. Transfusion of RBCs from such donors into nontransgenic but otherwise genetically identical recipient mice allows for the investigation of individual donor or recipient-specific variables that may impact RBC alloimmunization. Potential donor-related variables include methods of blood product collection, processing and storage, donor-specific characteristics, RBC antigen-specific factors, and others. Potential recipient-related variables include genetic factors (MHC/HLA type and polymorphisms of immunoregulatory genes), immune activation status, phenotype of regulatory immune cell subsets, immune cell functional characteristics, prior antigen exposures, and others. Although murine models are not perfect surrogates for human biology, these models generate phenomenological and mechanistic hypotheses of RBC alloimmunization and lay the groundwork for follow-up human studies. Long-term goals include improving transfusion safety and minimizing the morbidity/mortality associated with RBC alloimmunization.

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Section: Recipient Factorsmentioning

confidence: 99%

Section: Recipient Factorsmentioning

confidence: 99%

Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

Ryder

Zimring

Hendrickson

2014

Transfus Med Hemother

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show abstract

“…2 In humans, several genotypes of class II major histocompatibility complex (MHC II) could be implicated in alloimmunization against specific antigens but controversy remains regarding this. 3,4 Little is known about the role of CD4 + T cells in alloimmunization, 5 except for Treg cells. [6][7][8] Recently, we showed that the phenotype of CD4 + T cells from SCD patients differs according to whether M urine models of red blood cell transfusion show that inflammation associated with viruses or methylated DNA promotes red blood cell alloimmunization.…”

Section: Introductionmentioning

confidence: 99%

Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

et al. 2015

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“…Stephen and colleagues have addressed the issue of prophylaxis in antiKmediated HDFN using an elegant approach [13]. These authors first screened K peptides against mononuclear cells from Knegative women who had produced antiK to identify immunogenic K peptides.…”

Section: Solving the Dilemma Of Prevention Of Red Cell Alloimmunizationmentioning

confidence: 99%

Solving the Dilemma of Prevention of Red Cell Alloimmunization

Branch¹

2012

Immunotherapy

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Evaluation of: Stephen J, Cairns LS, Pickford WJ, Vickers MA, Urbaniak SJ, Barker RN. Identification, immunomodulatory activity and immunogenicity of the major helper T cell epitope on the K blood group antigen. Blood 119(23), 5563–5574 (2012). Alloimmunization to blood group antigens is a major concern in transfusion medicine. This occurs when antigen-mismatched blood is transfused into a recipient lacking a red blood cell antigen that is expressed on the donor red blood cells. Alloimmunization in this case can result in future problems in finding compatible blood for transfusion and can cause hemolytic transfusion reactions. Alloimmunization can also occur in instances where a mother lacks a red blood cell antigen that is carried by the fetus. In these cases, alloimmunization can result in an antibody that can cross the placenta and cause moderate-to-severe problems in the fetus or newborn due to hemolytic anemia and/or inhibition of hematopoiesis. This is called hemolytic disease of the fetus and newborn. Stephen et al. describe a unique approach to producing a peptide tolerogen to prevent alloimmunization to a specific blood group antigen, K, in the Kell blood group system. They identify an immunodominant K peptide and use this peptide to show that it strongly stimulates human T helper cells from K-immunized people in vitro and that it shows efficacy when used as a nasal tolerogen to suppress immunization with K protein in a mouse model. These results open the door for therapies aimed at the prevention and/or treatment of alloimmunization in both a transfusion setting and, importantly, in hemolytic disease of the fetus and newborn.

show abstract

Identification, immunomodulatory activity, and immunogenicity of the major helper T-cell epitope on the K blood group antigen

Cited by 32 publications

References 40 publications

Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

Factors Influencing RBC Alloimmunization: Lessons Learned from Murine Models

Red blood cell alloimmunization is influenced by the delay between Toll-like receptor agonist injection and transfusion

Solving the Dilemma of Prevention of Red Cell Alloimmunization

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