PMID- 38000035 OWN - NLM STAT- MEDLINE DCOM- 20231127 LR - 20240210 IS - 2375-2548 (Electronic) IS - 2375-2548 (Linking) VI - 9 IP - 47 DP - 2023 Nov 24 TI - Accurate prediction of HLA class II antigen presentation across all loci using tailored data acquisition and refined machine learning. PG - eadj6367 LID - 10.1126/sciadv.adj6367 [doi] LID - eadj6367 AB - Accurate prediction of antigen presentation by human leukocyte antigen (HLA) class II molecules is crucial for rational development of immunotherapies and vaccines targeting CD4(+) T cell activation. So far, most prediction methods for HLA class II antigen presentation have focused on HLA-DR because of limited availability of immunopeptidomics data for HLA-DQ and HLA-DP while not taking into account alternative peptide binding modes. We present an update to the NetMHCIIpan prediction method, which closes the performance gap between all three HLA class II loci. We accomplish this by first integrating large immunopeptidomics datasets describing the HLA class II specificity space across all loci using a refined machine learning framework that accommodates inverted peptide binders. Next, we apply targeted immunopeptidomics assays to generate data that covers additional HLA-DP specificities. The final method, NetMHCIIpan-4.3, achieves high accuracy and molecular coverage across all HLA class II allotypes. FAU - Nilsson, Jonas B AU - Nilsson JB AUID- ORCID: 0000-0002-1322-2644 AD - Department of Health Technology, Technical University of Denmark, DK-2800 Lyngby, Denmark. FAU - Kaabinejadian, Saghar AU - Kaabinejadian S AUID- ORCID: 0000-0002-8434-8703 AD - Pure MHC LLC, Oklahoma City, OK, USA. AD - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. FAU - Yari, Hooman AU - Yari H AUID- ORCID: 0000-0002-8285-7985 AD - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. FAU - Kester, Michel G D AU - Kester MGD AUID- ORCID: 0000-0002-8960-7348 AD - Department of Hematology, Leiden University Medical Center, Leiden, Netherlands. FAU - van Balen, Peter AU - van Balen P AUID- ORCID: 0000-0002-9670-4664 AD - Department of Hematology, Leiden University Medical Center, Leiden, Netherlands. FAU - Hildebrand, William H AU - Hildebrand WH AUID- ORCID: 0000-0002-7066-4174 AD - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. FAU - Nielsen, Morten AU - Nielsen M AUID- ORCID: 0000-0001-7885-4311 AD - Department of Health Technology, Technical University of Denmark, DK-2800 Lyngby, Denmark. LA - eng GR - 75N93019C00001/AI/NIAID NIH HHS/United States GR - U24 CA248138/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20231124 PL - United States TA - Sci Adv JT - Science advances JID - 101653440 RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DP Antigens) RN - 0 (HLA-DQ Antigens) RN - 0 (Peptides) SB - IM MH - Humans MH - *Antigen Presentation MH - *HLA-DR Antigens/metabolism MH - HLA-DP Antigens/chemistry MH - HLA-DQ Antigens/chemistry MH - Peptides/chemistry PMC - PMC10672173 EDAT- 2023/11/24 18:42 MHDA- 2023/11/27 12:43 PMCR- 2023/11/24 CRDT- 2023/11/24 14:03 PHST- 2023/11/27 12:43 [medline] PHST- 2023/11/24 18:42 [pubmed] PHST- 2023/11/24 14:03 [entrez] PHST- 2023/11/24 00:00 [pmc-release] AID - adj6367 [pii] AID - 10.1126/sciadv.adj6367 [doi] PST - ppublish SO - Sci Adv. 2023 Nov 24;9(47):eadj6367. doi: 10.1126/sciadv.adj6367. Epub 2023 Nov 24.