HLABrew for Human Leukocyte Antigen Class I-Presented Epitope Recognition and Mimotope Discovery.

Accurate identification of human leukocyte antigen (HLA) class I-presented epitopes is essential for developing personalized vaccines and immunotherapies. Here, we present HLABrew, a unified deep learning framework for HLA class I epitope prediction and allele-specific mimotope design. By integrating the Transformer, variational autoencoder, and dual cross-attention, HLABrew achieves state-of-the-art performance with hierarchical and allele-aware representations. HLABrew accurately deconvolves multiallelic immunopeptidomics data to recover allele-specific binding motifs and expand epitope coverage. Leveraging its generative capacity, HLABrew further designs mimotopes guided by learned peptide-HLA binding preferences, with the potential to enhance antigen presentation and provide candidates for downstream immunogenicity evaluation.