Anti-HLA-A monoclonal antibody, clone NFN-234

Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA class I-associated peptides across a large fraction of the human population, we used mass spectrometry to profile >185,000 peptides eluted from 95 HLA-A, -B, -C and -G mono-allelic cell lines. We identified canonical peptide motifs per HLA allele, unique and shared binding submotifs across alleles and distinct motifs associated with different peptide lengths. By integrating these data with transcript abundance and peptide processing, we developed HLAthena, providing allele-and-length-specific and pan-allele-pan-length prediction models for endogenous peptide presentation. These models predicted endogenous HLA class I-associated ligands with 1.5-fold improvement in positive predictive value compared with existing tools and correctly identified >75% of HLA-bound peptides that were observed experimentally in 11 patient-derived tumor cell lines.

Background The human leukocyte antigen (HLA)-B*13:01 was reported as an important risk factor for dapsone hypersensitivity syndrome (DHS) in Chinese and Thai populations. Research design and methods From the Korean nationwide registry, seven subjects with previous DHS were included. Their HLA allele/phenotype frequencies were compared with 8 dapsone-tolerant subjects recruited from a single institution, and general population (n = 485) in Korea. The authors also performed a meta-analysis with these data using previous Chinese and Thai studies. Results Among the seven DHS subjects, 85.7% presented with the HLA-B*13:01 allele. The HLA-C*03:04, HLA-DRB1*12:02 (both in linkage disequilibrium with HLA-B*13:01), and HLA-A*02:01 alleles were also presented in 85.7%, 71.4%, and 71.4%, respectively. Subjects with HLA-B*13:01 were susceptible to developing DHS compared to dapsone-tolerant controls (odds ratio [OR]: 73.667) and the Korean general population (OR: 139.500). HLA-C*03:04 (OR: 40.935), HLA-DRB*12:02 (OR: 36.613), and HLA-A*02:01 (OR: 5.862) showed similar results. In meta-analysis, HLA-B*13:01 was associated with dapsone-induced hypersensitivity (overall OR: 42.692), and subgroup analyses according to the control types demonstrated similar results (OR:43.694 and 41.866, respectively). Conclusions Similar to previous Asian population studies, HLA-B*13:01 is significantly associated with the risk of DHS in Korea. These associations may be useful for preventing DHS and improving drug safety.