5Peptide Binding motif Height of a column equal to I Relative height of a letter is pHLA-A0201High informationpositions
6NetMHC-3.0 www.cbs.dtu.dk/services/NetMHC 62 ANN and 68 PSSMCovering Human, Primate and Mouse MHCPredictions can be made for 8-11 mer petides
7HLA polymorphism< 50 HLA alleles are characterized by binding dataReliable MHC class I binding predictions (NetMHC-3.0) for 60 HLA A and B moleculesNo methods for HLA-C, and HLA-ELong way to over 1500!
8Few human beings will share the same set of HLA alleles HLA polymorphismFew human beings will share the same set of HLA allelesDifferent persons will react to a pathogen infection in a non-similar mannerA CTL based vaccine must include epitopes specific for each HLA allele in a populationA CTL based vaccine must consist of ~1000 HLA class I epitopes and ~5000 class II epitopes
13HLA polymorphism!B1513B3811A3106B3912B5102A3107B3709A2314A7411A0216A3108A2405B4052B4408B4426A0302B4036B5901A2904A3015B1515B4422A0273B4403B5207B3514B1578A6824B2724B5605A2458B0709A2442Random subset of 4% of the allele in the previous slide. To illustrate how sparsely we have sampled the polymorphism
14HLA polymorphismThe IMGT/HLA Sequence Database currently encompass more than 1500 HLA class I proteinsSource:However, we have been outpaced by the HLA discovery rate; our goal becomes more distant and elusive
15Supertypes. What are they good for? Alleles with in supertypes present the same set of peptides!Is this really so?Less that 50% of A6802 binders will bind to A0201!Less than 33% of A0201 binders will bind to A6802!
20Pan-specific methodInclude polymorphic residues in potential contact with the bound peptideThe contact residues are defined as being within 4.0 Å of the peptide in any of a representative set of HLA-A and -B structures with nonamer peptides.Only polymorphic residues from A, B, and C alleles are includedPseudo-sequence consisting of 34 amino acid residues.
41MHC pseudo sequenceInclude polymorphic residues in potential contact with the bound peptideThe contact residues are defined as being within 4.0 Å of the peptide in any of a representative set of HLA-DR, -DQ, and DP structures with peptides.Only polymorphic residues are includedPseudo-sequence consisting of 25 amino acid residues.