Proteome Sampling by the HLA Class I Antigen Processing Pathway 英文参考文献.docVIP

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Proteome Sampling by the HLA Class I Antigen Processing Pathway 英文参考文献.doc

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Proteome Sampling by the HLA Class I Antigen Processing Pathway 英文参考文献

ProteomeSamplingbytheHLAClassIAntigen ProcessingPathway IlkaHoof1*,DebbievanBaarle2,WilliamH.Hildebrand3,CanKes?mir1 1Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands, 2Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands,3DepartmentofMicrobiologyandImmunology,UniversityofOklahomaHealthSciencesCenter,OklahomaCity,Oklahoma,UnitedStatesofAmerica Abstract The peptide repertoire that is presented by the set of HLA class I molecules of an individual is formed by the different playersoftheantigenprocessingpathwayandthestringentbindingenvironmentoftheHLAclassImolecules.Peptide elutionstudieshaveshownthatonlyasubsetofthehumanproteomeissampledbytheantigenprocessingmachineryand represented on the cell surface. In our study, we quantified the role of each factor relevant in shaping the HLA class I peptiderepertoirebycombiningpeptideelutiondata,insilicopredictionsofantigenprocessingandpresentation,anddata ongeneexpressionandproteinabundance.Ourresultsindicatethatgeneexpressionlevel,proteinabundance,andrateof potentialbindingpeptidesperproteinhaveaclearimpactonsamplingprobability.Furthermore,onceaproteinisavailable fortheantigenprocessingmachineryinsufficientamounts,C-terminalprocessingefficiencyandbindingaffinitytotheHLA class I molecule determine the identity of the presented peptides. Having studied the impact of each of these factors separately,wesubsequentlycombinedallfactorsinalogisticregressionmodelinordertoquantifytheirrelativeimpact. This model demonstrated the superiority of protein abundance over gene expression level in predicting sampling probability.Beingabletodiscriminatebetweensampledandnon-sampledproteinstoasignificantdegree,ourapproach canpotentiallybeusedtopredictthesamplingprobabilityofselfproteinsandofpathogen-derivedproteins,whichisof importancefortheidentificationofautoimmuneantigensandvaccinationtargets. Citation: Hoof I, van Baarle D,Hildebrand WH, Kes?mir C(2012) Proteome Sampling by