Differential immunogenicity of HLA mismatches: HLA-A2 versus HLA-A28

Dankers, Marlies K.A.; Roelen, Dave L.; Meer-Prins, E.M.W. van der; Lange, Peter de; Korfage, Nelleke; Smits, Jacqueline M.; Persijn, G. G.; Welsh, Ken I.; Doxiadis, Ilias I.N.; Claas, Frans H.J.

doi:10.1097/01.tp.0000044456.51462.e2

Cited by 17 publications

(16 citation statements)

References 9 publications

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“…HLA molecules are not equally immunogenic, and some are more likely to initiate a humoral rather than a cellular immune response [25]. The relative immunogenicity is not an intrinsic property of a particular donor HLA molecule, but must be considered in the context of recipient HLA [26,27]. HLA epitopes recognised by alloantibodies are composed of three amino acids (triplets).…”

Section: Antigen and Alloantibody Formation In Transplantationmentioning

confidence: 99%

The generation and maintenance of serum alloantibody

Clatworthy

Espéli

Torpey

et al. 2010

Current Opinion in Immunology

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Donor-specific alloantibodies (DSA) mediate hyperacute and acute antibody-mediated rejection (AMR), which can lead to early graft damage and loss, and are also associated with chronic AMR and reduced long-term graft survival. Such alloantibodies can be generated by previous exposure to major histocompatibility (MHC) antigens (usually via blood transfusions, previous allografts or pregnancy) or can occur de novo after transplantation. Recent studies also suggest that non-MHC antibodies, including those recognising major histocompatibility complex class I-related chain A (MICA), MICB, vimentin, angiotensin II type I receptor may also have an adverse impact on allograft outcomes. In this review, we consider how the dose, route and context of antigen exposure influences DSA induction and describe factors which control the generation, maintenance and survival of alloantibody-producing plasma cells. Finally, we discuss the implications of these variables on therapeutic approaches to DSA.

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Section: Antigen and Alloantibody Formation In Transplantationmentioning

confidence: 99%

The generation and maintenance of serum alloantibody

Clatworthy

Espéli

Torpey

et al. 2010

Current Opinion in Immunology

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“…The immunogenicity of individual HLA mismatches is highly diverse; some mismatched HLA molecules lead to sensitization significantly more frequently than other HLA molecules (8,10,27). We investigated whether the immunogenicity of individual HLA molecules could be explained by the number of PIRCHE-II.…”

Section: The Immunogenicity Of Individual Hla Mismatches Cannot Be Exmentioning

confidence: 99%

Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy

Geneugelijk

Hönger

Deutekom

et al. 2015

American Journal of Transplantation

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† Contributed equally. ‡ Contributed equally.Pregnancy can prime maternal immune responses against inherited paternal HLA of the fetus, leading to the production of child-specific HLA antibodies. We previously demonstrated that donor-specific HLA antibody formation after kidney transplantation is associated with donor-derived HLA epitopes presented by recipient HLA class II (predicted indirectly recognizable HLA epitopes presented by HLA class II [PIRCHE-II]). In the present study, we evaluated the role of PIRCHE-II in child-specific HLA antibody formation during pregnancy. A total of 229 mother-child pairs were HLA typed. For all mismatched HLA class I molecules of the child, we subsequently predicted the number of HLA epitopes that could be presented by maternal HLA class II molecules. Child-specific antigens were classified as either immunogenic or nonimmunogenic HLA based on the presence of specific antibodies and correlated to PIRCHE-II numbers. Immunogenic HLA contained higher PIRCHE-II numbers than nonimmunogenic HLA. Moreover, the probability of antibody production during pregnancy increased with the number of PIRCHE-II. In conclusion, our data suggest that the number of PIRCHE-II is related to the formation of child-specific HLA antibodies during pregnancy. Present confirmation of the role of PIRCHE-II in antibody formation outside the transplantation setting suggests the PIRCHE-II concept is universal.Abbreviations: IPA, inherited paternal HLA antigens; MFI, mean fluorescence intensity; PIRCHE-II, predicted indirectly recognizable HLA epitopes presented by HLA class II; SAB, single HLA antigen beads

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“…Recently, mismatches between HLA-A alloantigens were shown to generate differing magnitudes of alloreactivity suggesting a hierarchical nature of the response (35,39). Therefore, dissection of individual HLA alloantigenic contributions to the total T-cell alloresponse provides an opportunity to evaluate both the strength of alloreactivity and the relative importance of specific mismatched antigens.…”

Section: Introductionmentioning

confidence: 99%

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Mifsud

Purcell

Chen

et al. 2008

American Journal of Transplantation

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Allogeneic solid organ transplantation often occurs across multiple donor-recipient HLA mismatches with consequent risk of allograft rejection. However, there is growing evidence that not all HLA mismatches are equivalent in their stimulation of allogeneic T cells making it important to determine which of these might be more significant as predictors of allograft rejection. To this end, we used defined antigen-presenting cell (APC) transfectants expressing single MHC-I allotypes as target cells that could discriminate the relative contribution of individual mismatched MHC-I allotypes to direct T-cell alloreactivity. We demonstrate remarkably reproducible patterns of immunodominance in reactivity across mismatched MHC-I allotypes. These patterns are HLA context-dependent, partly reflecting alloantigenic competition in responder cell responses. In strong alloresponses, we also observed an increased percentage of alloreactive T CD8 cells in female responders, regardless of the stimulator gender, highlighting HLA-independent factors in the potency of the alloresponse. This approach provides a potential measure of specific alloreactive T cells that could be used in clinical practice for selection of donors, assessment of posttransplant outcomes, modulation of immunosuppression and detection of rejection episodes.

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Differential immunogenicity of HLA mismatches: HLA-A2 versus HLA-A28

Cited by 17 publications

References 9 publications

The generation and maintenance of serum alloantibody

The generation and maintenance of serum alloantibody

Predicted Indirectly Recognizable HLA Epitopes Presented by HLA-DRB1 Are Related to HLA Antibody Formation During Pregnancy

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

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