Table 5. Overview of different... | American Society of Hematology

Table 5.

Overview of different permissible matching strategies

Name	Strategy	Possible biology
HLAMatchmaker (Duquesnoy et al^16,17)	Identification of amino acid triplets present in HLA that are mismatched at known accessible/polymorphic positions. Special attention to triplets confirmed to have been binding sites for donor-specific antibodies. Interlocus comparisons are performed.	Triplets accessible on the cell surface (eplets/epitopes) may lead to donor-specific antibody formation and solid organ transplant rejection.
PIRCHE (Stenger et al¹⁴)	Identification of mismatching peptide fragments derived from HLA, which can also be presented in HLA class I (PIRCHE-I) or class II (PIRCHE-II).	Presentation of HLA-derived nonself peptides may lead to indirect allorecognition and both aGVHD and rejection.
PBM matching (Crivello et al³²)	Identification of mismatching peptide binding motif (PBM) categories, where PBM categories have been defined using hierarchical clustering on the peptide repertoire presented.	Differences in the PBM lead to a different peptide repertoire presented, against which T cells have not been tolerized. Distinct PBM clusters can be identified with a similar presented peptide repertoire. If these clusters match, there may be a reduction in indirect allorecognition.
HLA-EMMA (the present article)	Identification of single amino acids that are mismatched on specific positions within the HLA molecule. Special attention to α-helices and β-sheets. Interlocus comparisons are optional, but not applied in this study.	Alterations in the HLA molecule may lead to both changes in the peptide repertoire presented and the way the T-cell receptor docks to the HLA molecule and recognizes the presented peptide in the context of HLA. This may lead to both direct and indirect allorecognition. The α-helices are particularly important because they can directly affect both.

Name	Strategy	Possible biology
HLAMatchmaker (Duquesnoy et al^16,17)	Identification of amino acid triplets present in HLA that are mismatched at known accessible/polymorphic positions. Special attention to triplets confirmed to have been binding sites for donor-specific antibodies. Interlocus comparisons are performed.	Triplets accessible on the cell surface (eplets/epitopes) may lead to donor-specific antibody formation and solid organ transplant rejection.
PIRCHE (Stenger et al¹⁴)	Identification of mismatching peptide fragments derived from HLA, which can also be presented in HLA class I (PIRCHE-I) or class II (PIRCHE-II).	Presentation of HLA-derived nonself peptides may lead to indirect allorecognition and both aGVHD and rejection.
PBM matching (Crivello et al³²)	Identification of mismatching peptide binding motif (PBM) categories, where PBM categories have been defined using hierarchical clustering on the peptide repertoire presented.	Differences in the PBM lead to a different peptide repertoire presented, against which T cells have not been tolerized. Distinct PBM clusters can be identified with a similar presented peptide repertoire. If these clusters match, there may be a reduction in indirect allorecognition.
HLA-EMMA (the present article)	Identification of single amino acids that are mismatched on specific positions within the HLA molecule. Special attention to α-helices and β-sheets. Interlocus comparisons are optional, but not applied in this study.	Alterations in the HLA molecule may lead to both changes in the peptide repertoire presented and the way the T-cell receptor docks to the HLA molecule and recognizes the presented peptide in the context of HLA. This may lead to both direct and indirect allorecognition. The α-helices are particularly important because they can directly affect both.