Integral Use of Immunopeptidomics and Immunoinformatics for the Characterization of Antigen Presentation and Rational Identification of BoLA-DR-Presented Peptides and Epitopes

Author(s):Show less -

Fisch, Andressa ^[1] ; Reynisson, Birkir ^[2] ; Benedictus, Lindert ^[3] ; Nicastri, Annalisa ^[4] ; Vasoya, Deepali ^[3] ; Morrison, Ivan ^[3] ; Buus, Soren ^[5] ; Ferreira, Beatriz Rossetti ^[1] ; Santos, Isabel Kinney Ferreira de Miranda ^[6] ; Ternette, Nicola ^[4] ; Connelley, Tim ^[3] ; Nielsen, Morten ^{[2, 7]}

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Coll Nursing, Av Bandeirantes, Ribeirao Preto - Brazil

^[2] Tech Univ Denmark, Dept Hlth Technol, Lyngby - Denmark

^[3] Roslin Inst, Edinburgh, Midlothian - Scotland

^[4] Jenner Inst, Nuffield Dept Med, Oxford - England

^[5] Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Lab Expt Immunol, Copenhagen - Denmark

^[6] Univ Sao Paulo, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil

^[7] Univ Nacl San Martin, Inst Invest Biotecnol, San Martin - Argentina

• Document type: Journal article
• Source: JOURNAL OF IMMUNOLOGY; v. 206, n. 10, p. 2489-2497, MAY 15 2021.
• Web of Science Citations: 0

Abstract

MHC peptide binding and presentation is the most selective event defining the landscape of T cell epitopes. Consequently, understanding the diversity of MHC alleles in a given population and the parameters that define the set of ligands that can be bound and presented by each of these alleles (the immunopeptidome) has an enormous impact on our capacity to predict and manipulate the potential of protein Ags to elicit functional T cell responses. Liquid chromatography-mass spectrometry analysis of MHC-eluted ligand data has proven to be a powerful technique for identifying such peptidomes, and methods integrating such data for prediction of Ag presentation have reached a high level of accuracy for both MHC class I and class II. In this study, we demonstrate how these techniques and prediction methods can be readily extended to the bovine leukocyte Ag class II DR locus (BoLA-DR). BoLA-DR binding motifs were characterized by eluted ligand data derived from bovine cell lines expressing a range of DRB3 alleles prevalent in Holstein-Friesian populations. The model generated (NetBoLAIIpan, available as a Web server at www.cbs.dtu.dk/services/NetBoLAIIpan) was shown to have unprecedented predictive power to identify known BoLA-DR-restricted CD4 epitopes. In summary, the results demonstrate the power of an integrated approach combining advanced mass spectrometry peptidomics with immunoinformatics for characterization of the BoLA-DR Ag presentation system and provide a prediction tool that can be used to assist in rational evaluation and selection of bovine CD4 T cell epitopes. (AU)

• FAPESP's process: 18/23579-8 - Development of a recombinant multicomponent chimeric vaccine based in protein epitopes from Rhipicephalus microplus ticks
• Grantee: Andressa Fisch
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/09683-9 - Development of a recombinant multicomponent chimeric vaccine based in protein epitopes from Rhipicephalus microplus ticks
• Grantee: Beatriz Rossetti Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/21401-4 - Seeking vaccine antigen epitopes presented by BoLA-DR for development of a multi epitope-based vaccine against R. microplus tick infestations
• Grantee: Andressa Fisch
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate