biostudies-literature00540Martin PJNCI NIH HHSHealth Resources and Services AdministrationNational Institutes of HealthOffice of Naval Research782152https://www.ebi.ac.uk/biostudies/studies/S-EPMC8636906biostudies-literatureUnknown12Minor histocompatibility antigens (mHAg) composed of peptides presented by HLA molecules can cause immune responses involved in graft-versus-host disease (GVHD) and graft-versus-leukemia effects after allogeneic hematopoietic cell transplantation (HCT). The current study was designed to identify individual graft-versus-host genomic mismatches associated with altered risks of acute or chronic GVHD or relapse after HCT between HLA-genotypically identical siblings. Our results demonstrate that in allogeneic HCT between a pair of HLA-identical siblings, a mHAg manifests as a set of peptides originating from annotated proteins and non-annotated open reading frames, which i) are encoded by a group of highly associated recipient genomic mismatches, ii) bind to HLA allotypes in the recipient, and iii) evoke a donor immune response. Attribution of the immune response and consequent clinical outcomes to individual peptide components within this set will likely differ from patient to patient according to their HLA types.Frontiers in immunologyA Model of Minor Histocompatibility Antigens in Allogeneic Hematopoietic Cell Transplantation.PMC8636906P30 CA015704N00014-20-1-2705 , N00014-20-1-2832U24 CA076518AI33484, AI149213, CA015704, CA18029, HL087690, HL088201, HL094260 , HL105914, U24CA076518 , P30 CA015704Heavner BZheng XMartin PJLevine DMNorris BMGeraghty DEStorer BESather CLSpellman SRWu FHansen JAJain D54falseA Model of Minor Histocompatibility Antigens in Allogeneic Hematopoietic Cell Transplantation.Minor histocompatibility antigens (mHAg) composed of peptides presented by HLA molecules can cause immune responses involved in graft-versus-host disease (GVHD) and graft-versus-leukemia effects after allogeneic hematopoietic cell transplantation (HCT). The current study was designed to identify individual graft-versus-host genomic mismatches associated with altered risks of acute or chronic GVHD or relapse after HCT between HLA-genotypically identical siblings. Our results demonstrate that in allogeneic HCT between a pair of HLA-identical siblings, a mHAg manifests as a set of peptides originating from annotated proteins and non-annotated open reading frames, which i) are encoded by a group of highly associated recipient genomic mismatches, ii) bind to HLA allotypes in the recipient, and iii) evoke a donor immune response. Attribution of the immune response and consequent clinical outcomes to individual peptide components within this set will likely differ from patient to patient according to their HLA types.2021-01-01T00:00:00Z20212024-11-19T22:57:07.377Z2022-02-11T14:17:19.169ZS-EPMC86369063486805810.3389/fimmu.2021.782152