PMID- 34937342 OWN - NLM STAT- MEDLINE DCOM- 20220228 LR - 20220228 IS - 1535-3907 (Electronic) IS - 1535-3893 (Linking) VI - 21 IP - 1 DP - 2022 Jan 7 TI - Abundance, Betweenness Centrality, Hydrophobicity, and Isoelectric Points Are Relevant Factors in the Processing of Parental Proteins of the HLA Class II Ligandome. PG - 164-171 LID - 10.1021/acs.jproteome.1c00662 [doi] AB - Adaptive cellular and humoral immune responses to infectious agents require previous recognition of pathogenic peptides bound to human leukocyte antigen (HLA) class II molecules exposed on the surface of the professional antigen-presenting cells. Knowledge of how these peptide ligands are generated is essential to understand the basis for CD4(+) T-cell-mediated immunity and tolerance. In this study, a high-throughput mass spectrometry analysis was used to identify more than 16,000 cell peptides bound to several HLA-DR and -DP class II molecules isolated from large amounts of uninfected and virus-infected human cells (ProteomeXchange accession: PXD028006). The analysis of the 1808 parental proteins containing HLA class II ligands revealed that these cell proteins were more acidic, abundant, and highly connected but less hydrophilic than non-parental proteomes. Therefore, the percentage of acidic residues was increased and hydroxyl and polar residues were decreased in the parental proteins for the HLA class II ligandomes versus the non-parental proteomes. This definition of the properties shared by parental proteins that constitute the source of the HLA class II ligandomes can serve as the basis for the development of bioinformatics tools to predict proteins that are most likely recognized by the immune system through the CD4(+) helper T lymphocytes in both autoimmunity and infection. FAU - Lorente, Elena AU - Lorente E AD - Unidad de Presentacion y Regulacion Inmunes, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. FAU - Martin-Galiano, Antonio J AU - Martin-Galiano AJ AD - Unidad de Infecciones Intrahospitalarias, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. FAU - Kadosh, Dganit Melamed AU - Kadosh DM AD - Department of Biology, Technion-Israel Institute of Technology, 32000 Haifa, Israel. FAU - Barriga, Alejandro AU - Barriga A AD - Unidad de Presentacion y Regulacion Inmunes, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. FAU - Garcia-Arriaza, Juan AU - Garcia-Arriaza J AD - Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas (CSIC), 28049 Madrid, Spain. FAU - Mir, Carmen AU - Mir C AD - Unidad de Presentacion y Regulacion Inmunes, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. FAU - Esteban, Mariano AU - Esteban M AD - Department of Molecular and Cellular Biology, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas (CSIC), 28049 Madrid, Spain. FAU - Admon, Arie AU - Admon A AUID- ORCID: 0000-0003-0504-3950 AD - Department of Biology, Technion-Israel Institute of Technology, 32000 Haifa, Israel. FAU - Lopez, Daniel AU - Lopez D AUID- ORCID: 0000-0003-0268-5878 AD - Unidad de Presentacion y Regulacion Inmunes, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20211222 PL - United States TA - J Proteome Res JT - Journal of proteome research JID - 101128775 RN - 0 (HLA Antigens) RN - 0 (HLA-DR Antigens) SB - IM MH - CD4-Positive T-Lymphocytes MH - *HLA Antigens/genetics/metabolism MH - *HLA-DR Antigens MH - Humans MH - Hydrophobic and Hydrophilic Interactions MH - Isoelectric Point MH - Parents OTO - NOTNLM OT - HLA OT - antigen presentation OT - ligand OT - mass spectrometry EDAT- 2021/12/24 06:00 MHDA- 2022/03/01 06:00 CRDT- 2021/12/23 05:20 PHST- 2021/12/24 06:00 [pubmed] PHST- 2022/03/01 06:00 [medline] PHST- 2021/12/23 05:20 [entrez] AID - 10.1021/acs.jproteome.1c00662 [doi] PST - ppublish SO - J Proteome Res. 2022 Jan 7;21(1):164-171. doi: 10.1021/acs.jproteome.1c00662. Epub 2021 Dec 22.