PMID- 28871256 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 8 DP - 2017 TI - Human Leukocyte Antigen (HLA)-DRB1*15:01 and HLA-DRB5*01:01 Present Complementary Peptide Repertoires. PG - 984 LID - 10.3389/fimmu.2017.00984 [doi] LID - 984 AB - Human leukocyte antigen (HLA)-DR15 is a haplotype associated with multiple sclerosis. It contains the two DRB* genes DRB1*1501 (DR2b) and DRB5*0101 (DR2a). The reported anchor motif of the corresponding HLA-DR molecules was determined in 1994 based on a small number of peptide ligands and binding assays. DR2a could display a set of peptides complementary to that presented by DR2b or, alternatively, a similar peptide repertoire but recognized in a different manner by T cells. It is known that DR2a and DR2b share some peptide ligands, although the degree of similarity of their associated peptidomes remains unclear. In addition, the contribution of each molecule to the global peptide repertoire presented by the HLA-DR15 haplotype has not been evaluated. We used mass spectrometry to analyze the peptide pools bound to DR2a and DR2b, identifying 169 and 555 unique peptide ligands of DR2a and DR2b, respectively. The analysis of these sets of peptides allowed the refinement of the corresponding binding motifs revealing novel anchor residues that had been overlooked in previous analyses. Moreover, the number of shared ligands between both molecules was low, indicating that DR2a and DR2b present complementary peptide repertoires to T cells. Finally, our analysis suggests that, quantitatively, both molecules contribute to the peptide repertoire presented by cells expressing the HLA-DR15 haplotype. FAU - Scholz, Erika Margaret AU - Scholz EM AD - Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, Bellaterra, Spain. AD - Immunology Unit, Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Spain. FAU - Marcilla, Miguel AU - Marcilla M AD - Proteomics Unit, Centro Nacional de Biotecnologia (CSIC), Madrid, Spain. FAU - Daura, Xavier AU - Daura X AD - Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, Bellaterra, Spain. AD - Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. FAU - Arribas-Layton, David AU - Arribas-Layton D AD - Benaroya Research Institute at Virginia Mason, Seattle, WA, United States. FAU - James, Eddie A AU - James EA AD - Benaroya Research Institute at Virginia Mason, Seattle, WA, United States. FAU - Alvarez, Inaki AU - Alvarez I AD - Institut de Biotecnologia i de Biomedicina, Universitat Autonoma de Barcelona, Bellaterra, Spain. AD - Immunology Unit, Department of Cell Biology, Physiology and Immunology, Universitat Autonoma de Barcelona, Bellaterra, Spain. LA - eng PT - Journal Article DEP - 20170821 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC5566978 OTO - NOTNLM OT - binding motif OT - human leukocyte antigen-DR OT - mass spectrometry OT - multiple sclerosis OT - peptidome EDAT- 2017/09/06 06:00 MHDA- 2017/09/06 06:01 PMCR- 2017/01/01 CRDT- 2017/09/06 06:00 PHST- 2017/06/06 00:00 [received] PHST- 2017/08/02 00:00 [accepted] PHST- 2017/09/06 06:00 [entrez] PHST- 2017/09/06 06:00 [pubmed] PHST- 2017/09/06 06:01 [medline] PHST- 2017/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2017.00984 [doi] PST - epublish SO - Front Immunol. 2017 Aug 21;8:984. doi: 10.3389/fimmu.2017.00984. eCollection 2017.