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#61
DEFINITION OF ALLELE-SPECIFIC PEPTIDE MOTIFS TO ESTIMATE THE SEVERITY OF HLA MISMATCHES .
Christina Bade-Doeding, Holger-Andreas Elsner, Dr., Britta Eiz-Vesper, Prof., Axel Seltsam, Prof. and Rainer Blasczyk, Prof.. Hannover Germany, Hannover Medical School, 30625, Transfusion Medicine.

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In this study we have sequenced peptides eluted from truncated recombinant HLA-A*6602 and A*6603 molecules, and compared their features with data reported for peptides presented by A*6601. The A*6601 allele differs from A*6602 by two amino acid (AA) exchanges at positions 90 (outer loop) and 163 (pocket A). A*6603 differs from both alleles by an additional exchange at position 70 (pockets A and B). There were no significant differences in the peptide motifs of A*6602 and A*6603, suggesting a minor importance for the exchange Gln70His, with both AA having neutral side-chains. However, we observed a striking difference at the auxiliary anchor P1 of peptides bound by A*6601 (polar/acidic AA: Asp, Glu) and A*6602/6603 (polar/ neutral AA: Ser) which interacts with pocket A. This finding may be best explained by the exchange Arg163Glu which results in a shift towards higher acidity in pocket A of A*6602/6603, apparently leading to the loss of preference for acidic auxiliary anchors. In conclusion, the similar peptide motifs of A*6602 and A*6603 suggest low allogenicity when these alleles are mismatched in stem cell transplantation; whereas differences in the peptide motif suggest the opposite for the mismatch A*6601 vs. A*6602/6603. This knowledge about allele-specific peptide motifs will contribute to the ranking of HLA subtype mismatches in the donor selection process, when no HLA-identical donor is available.