The Effect of Individual Hla-a and -B Mismatches on the Generation of Cytotoxic T Lymphocyte Precursors

Zhang, L.; Bree, Simone van; Rood, Jon J. van; Claas, Frans H.J.

doi:10.1097/00007890-199012000-00022

Cited by 19 publications

(9 citation statements)

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“…Higher CTLp frequencies across mismatched HLA-B antigens suggested these may be more immunogenic than other MHC-I isotypes (34)(35)(36), consistent with the finding that mismatched HLA-B antigens are more influential in contributing to renal allograft survival than mismatched HLA-A antigens (37,38). Recently, mismatches between HLA-A alloantigens were shown to generate differing magnitudes of alloreactivity suggesting a hierarchical nature of the response (35,39).…”

Section: Introductionsupporting

confidence: 70%

“…It is well known that some MHC-I mismatches are more clinically important than others (6,7). Thus, interlocus (A vs. B) (34)(35)(36)(37)(38) and intralocus hierarchies of immunogenicity have been described, including HLA-A2 (48,49), HLA-A2 and -A28 (39), HLA-B27 (50,51), HLA-B35 (52) and HLA-B44 (33,(53)(54)(55). However, it has proved difficult to predict which MHC mismatches might be most relevant to allograft survival.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Introductionsupporting

confidence: 70%

Section: Discussionmentioning

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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“…The fact that allogeneic responses mediated by HLA-B are the only responses that significantly affect cell killing and proliferation can partly be explained by the increase in precursor frequency observed against HLA-B alleles relative to HLA-A demonstrated in former studies by others [27, 28] . Why HLA-B alleles have an increase in precursor frequency as shown by others and why this results in diminished killing of matched HLA-B targets is not clear.…”

Section: Resultsmentioning

confidence: 99%

Brief Report

Sabbaj¹,

Scanlon

et al. 2016

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Epidemiologic studies have demonstrated that HIV-1 discordant couples who share HLA-B alleles were more likely to transmit HIV-1. These data lead us to hypothesize that individuals who match at both HLA-B alleles should have a reduced allogeneic response than those who are not matched. We observed diminished killing of CD4+ target cells only when HLA-B alleles were matched. We propose that for cell-associated HIV-1 transmission the ability of the recipient to eliminate infected cells from a donor partner may be enhanced when HLA-B alleles are different between partners. These findings suggest a novel mechanism for protection against HIV infection.

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“…Studies on the population level have shown that the cytotoxic T lymphocyte precursor (CTLp) frequencies for HLA-B mismatches are significantly higher than CTLp frequencies against HLA-A [23]. A possible clinical relevance of these limiting dilution assays is suggested by the fact that in transplantation, mismatches for HLA-B seem to be more immunogenic and lead more often to graft rejection than mismatches for HLA-A.…”

Section: In Vitro Analysis Of Alloreactive T Cellsmentioning

confidence: 99%

Future HLA Matching Strategies in Clinical Transplantation

Claas

Roelen²,

Oudshoorn³

et al. 2002

Adequate HLA Matching in Keratoplasty

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Further developing this new line of permissible versus taboo mismatches, a new strategy will emerge for future HLA matching, which will not only suit a rare number of patients with frequent haplotypes but a great percentage of all patients. This principle of different immunogenicity of different mismatches can not only be applied to T-cell alloreactivity as shown here, but also to B-cell alloreactivity, where a recently developed computer algorithm (HLA matchmaker) can be instrumental in selecting donors with HLA mismatches, which do not lead to alloantibody formation.

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The Effect of Individual Hla-a and -B Mismatches on the Generation of Cytotoxic T Lymphocyte Precursors

Cited by 19 publications

References 0 publications

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

Brief Report

Future HLA Matching Strategies in Clinical Transplantation

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