5 Peptide Binding motif Height of a column equal to I Relative height of a letter is pHLA-A0201High informationpositions
6 NetMHC-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
7 HLA 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!
8 Few 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
13 HLA polymorphism!B1513B3811A3106B3912B5102A3107B3709A2314A7411A0216A3108A2405B4052B4408B4426A0302B4036B5901A2904A3015B1515B4422A0273B4403B5207B3514B1578A6824B2724B5605A2458B0709A2442Random subset of 4% of the allele in the previous slide. To illustrate how sparsely we have sampled the polymorphism
14 HLA 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
15 Supertypes. 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!
20 Pan-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.
41 MHC 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.