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THE FUTURE IS EPITOPES

THE FUTURE IS EPITOPES. DEREK MIDDLETON DAVID LOWE ROYAL LIVERPOOL UNIVERSITY HOSPITAL R. FP7 EC EUROSTAM. A EURO pe -wide S trategy to enhance T ransplantation of highly sensitized patients on basis of A cceptable HLA M ismatches. European populations on www.allelefrequencies.net.

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THE FUTURE IS EPITOPES

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  1. THE FUTURE IS EPITOPES DEREK MIDDLETON DAVID LOWE ROYAL LIVERPOOL UNIVERSITY HOSPITAL R

  2. FP7 EC EUROSTAM • A EUROpe-wide Strategy to enhance • Transplantation of highly sensitized patients • on basis of Acceptable HLA Mismatches

  3. European populations on www.allelefrequencies.net Europe: 208 HLA pops from 399,305 individuals

  4. Example of population frequencies in AFND Azores central Islands n=59

  5. Examples of Class I Epitopes • Epitopes are sorted according to their sequence positions in each locus • Distinct sequence position numbers and polymorphic residue descriptions with standard single letter amino acid codes, e.g. 62GE

  6. HLA Epitope Registry Website http://epregistry.ufpi.br • Total of 526 epitopes • Confirmed = 57 • Antibody Reactivity Data • Provisional = 103 • Partial Antibody Reactivity Data • Predicted = 366 • No Antibody Reactivity Data

  7. HLA Epitope Frequencies Molecular locations of epitopes in HLA-A24 molecule (Duquesnoy, 2011) • Epitope Frequencies in populations: • Estimate epitope frequencies for all populations stored in AFND • Link data with HLA Epitope Registry website

  8. Sum of Epitopes From Allele Frequencies vs. Frequency of Individuals Having the Epitope Two Loci One locus • Frequency of Individuals Expressing Epitope was calculated from HLA raw data • Using raw data is the most accurate way to determine Epitope Frequency in Populations Sum of Epitope Allele Count Count of Individuals Expressing Epitope

  9. HLA−A and −B Epitope Frequencies in World Populations Epitope Frequencies were obtained from raw genotyping data

  10. High Resolution Alleles from HLA-A*01 Antigenic Group by Epitopes in Position 9

  11. Estimation of epitope frequencies from haplotype data England North West Frequencies of epitopes obtained from raw genotyping data Frequencies of epitopes estimated from haplotype data

  12. Single Donor Mismatch; Donor A32, recipient A1 Donor mm: A32 9 Identified epitopes, none present on HLA-A1 167W 253Q 167W 253Q 109L+ 131R 80I 80I 138M+ 144Q 253Q 80I+ 109L 109L 109L Cw7 Cw6 A29 B57 A1 B8 A32 80I+ 82L+ 82L+ 109L+ 131R 109L+ 163T 109L+ 163T 138M+ 144Q 167W 167W 167W Recipient HLA

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