HLA-EMMA

HLA-EMMA analyzes HLA class I and class II amino acid sequences to identify solvent-accessible polymorphic mismatches between donors and recipients that may drive donor-specific antibody (DSA) formation.

Key Features:

• Amino-acid level comparison: Performs detailed comparisons of donor and recipient HLA class I and class II sequences at the amino acid level.
• Solvent-accessible mismatch identification: Identifies polymorphic amino acid mismatches that are solvent accessible and thus potentially exposed to B cell receptors.
• Simultaneous class I and II analysis: Compares both HLA class I and class II molecules in the same analysis to capture mismatches across loci.
• Batch processing capability: Processes numerous donor–recipient pairs concurrently for cohort-scale analyses.
• HLA Epitope Mismatch Algorithm: Implements the HLA Epitope Mismatch Algorithm (HLA-EMMA) logic to quantify immunogenic mismatches.

Scientific Applications:

• Renal transplantation risk assessment: Predicts immunogenic mismatches that are associated with de novo DSA formation and can inform graft-risk analyses in renal transplantation.
• Cohort immunogenicity studies: Enables large-cohort analyses to quantify frequencies of solvent-accessible mismatches across donor–recipient pairs.
• Validation of mismatch–DSA associations: Supports research validation such as the reported correlation between higher numbers of solvent-accessible amino acid mismatches and increased DSA formation in a study of 191 lymphocyte immunotherapy recipients.

Methodology:

Performs detailed amino-acid level comparisons of donor and recipient HLA class I and class II sequences and identifies polymorphic residues that are solvent accessible (surface-exposed) and thus accessible to B cell receptors.