Hla-b44.2 directed cytotoxic t cells associated with acute graft vs host disease following unrelated marrow transplantation

Keever, Carolyn A.; Leong, Nufatt; Cunningham, Isabel; Copelan, Ed; Avalos, Belinda R.; Klein, Jan; Kapoor, Neena; Tutschka, Peter J.

doi:10.1016/0198-8859(91)90255-8

Cited by 46 publications

(53 citation statements)

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“…In line with this notion, the nonconservative peptidebinding L156D difference between HLA-B*44:02 and HLA-B*44:03 was shown to be involved in rejection and GVHD after unrelated HCT. 60,61 It is tempting to speculate that the subsequent failure to confirm a predominant role of AA substitutions at position 156 for the outcome of unrelated HCT 18,20 might be related to the confounding effect of conservative substitutions at this position. For HLA-DPB1, AA substitutions at several of the positions covered by our FD AA scores have been shown to be important for in vitro T-cell allo-recognition and HCT outcome.…”

Section: Discussionmentioning

confidence: 99%

Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT

Crivello¹,

Heinold

Rebmann

et al. 2016

Blood

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Key Points• Nonpermissive mismatches associated with survival after HCT reflect FD between recipient-donor HLA-DPB1.• FD within HLA-DPB1 is determined by the combined impact of nonconservative peptide-binding AA substitutions.The role of HLA amino acid (AA) polymorphism for the outcome of hematopoietic cell transplantation (HCT) is controversial, in particular for HLA class II. Here, we investigated this question in nonpermissive HLA-DPB1 T-cell epitope (TCE) mismatches reflected by numerical functional distance (FD) scores, assignable to all HLA-DPB1 alleles based on the combined impact of 12 polymorphic AAs. We calculated the difference in FD scores (DFD) of mismatched HLA-DPB1 alleles in patients and their 10/10 HLA-matched unrelated donors of 379 HCTs performed at our center for acute leukemia or myelodysplastic syndrome. Receiver-operator curve-based stratification into 2 DFD subgroups showed a significantly higher percentage of nonpermissive TCE mismatches for DFD >2.665, compared with DFD £2.665 (88% vs 25%, P < .0001). In multivariate analysis, DFD >2.665 was significantly associated with overall survival (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.05-1.87; P < .021) and event-free survival (HR, 1.39; 95% CI, 1.05-1.82; P < .021), compared with DFD £2.665. These associations were stronger than those observed for TCE mismatches. There was a marked but not statistically significant increase in the hazards of relapse and nonrelapse mortality in the high DFD subgroup, whereas no differences were observed for acute and chronic graft-versus-host disease. Seven nonconservative AA substitutions in peptide-binding positions had a significantly stronger impact on DFD compared with 5 others (P 5 .0025), demonstrating qualitative differences in the relative impact of AA polymorphism in HLA-DPB1. The novel concept of DFD sheds new light onto nonpermissive HLA-DPB1 mismatches in unrelated HCT. (Blood. 2016;128(1):120-129)

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Section: Discussionmentioning

confidence: 99%

Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT

Crivello¹,

Heinold

Rebmann

et al. 2016

Blood

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“…Analysis of HLA-A2 mutants have confirmed the strong influence of position 156 on T cell recognition [22] but suggest a limited influence for this residue on peptide binding [23]. Macdonald et al [24] responses reflecting their barrier to hemopoietic stem cell transplantation [25,26]. Although these two alleles were shown to share >95% of their self-peptide repertoire, HLA-B*4403 presents more unique selfpeptides than B*4402.…”

Section: Peptide-mhc Binding Kinetics Correlates With Epitope Immunogmentioning

confidence: 99%

The impact of HLA‐B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV

et al. 2007

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The factors controlling epitope selection in the T cell response to persistent viruses are not fully understood, and we have examined this issue in the context of four HLA-B*35-binding peptides from the pp65 antigen of human cytomegalovirus, two of which are previously undescribed. Striking differences in the hierarchy of immunodominance between these four epitopes were observed in healthy virus carriers expressing HLA-B 195 . By comparing peptide-MHC association and disassociation rates with peptide immunogenicity, it was clear that dissociation rates correlate more closely with the hierarchy of immunodominance among the four pp65 peptides. These findings demonstrate that MHC micropolymorphism at positions outside the primary anchor residue binding pockets can have a major impact on determinant selection in antiviral T cell responses. Such influences may provide the evolutionary pressure that maintains closely related MHC molecules in diverse human populations.

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“…The sequence originally designated B*440 1 has now been found to contain errors and be identical to the corrected sequence for B*4402, (E. Petersdorf personal communication) (48,49). Accordingly the name B*4401 has now been officially dropped.…”

Section: B New Allele Namesmentioning

confidence: 99%

Nomenclature for factors of the HLA system, 1994

Bodmer¹,

Marsh²,

Albert³

et al. 1994

Tissue Antigens

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248

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Hla-b44.2 directed cytotoxic t cells associated with acute graft vs host disease following unrelated marrow transplantation

Cited by 46 publications

References 0 publications

Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT

Functional distance between recipient and donor HLA-DPB1 determines nonpermissive mismatches in unrelated HCT

The impact of HLA‐B micropolymorphism outside primary peptide anchor pockets on the CTL response to CMV

Nomenclature for factors of the HLA system, 1994

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