COMBINATION OF RESIDUES LOCATED IN THE ALPHA HELICAL, CONECTING LOOPS AND/OR BETA SHEETS OF THE HLA-CLASS I MOLECULES DETERMINE HLA CLASS I SEROLOGIC EPITOPES.

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COMBINATION OF RESIDUES LOCATED IN THE ALPHA HELICAL, CONECTING LOOPS AND/OR BETA SHEETS OF THE HLA-CLASS I MOLECULES DETERMINE HLA CLASS I SEROLOGIC EPITOPES.
Martin Maiers , Geziena G.T. Schreuder , Arend Mulder , Jar How Lee , Martin Gutierrez , Carol Machan , Hugo A. Araujo , Edmond J. Yunis and Marcelo A. Fernandez-Vina . Minneapolis MI, National Marrow Donor Program, Information Systems ; Leiden Netherlands, Leiden University Medical center ; Canoga Park CA, One Lambda, Inc. ; Washington DC, Georgetown University, Department of Oncology and CW Bill Young DoD Marrow Donor Program and Boston MA, Harvard University, Dana Farber Cancer Institute .

A computational strategy was developed to correlate the reactivity of mAb with amino acid residues on the HLA class I molecules. This approach allows the mapping of putative epitopes (pEp). A set of 274 mAb from the 13^th IHWC was tested against 710 HLA-A/B allele-level typed cells. The mAb were classified according to the location of the mapped residues: 1) pEp with amino acids mapped on “alpha-helical/connecting loop” (AlCo); 2) pEp whose residues are found on both AlCo and binding groove(Gr). We mapped pEp for 268 mAb reactive with products of A- locus (n=109) or B-locus (n=159). Ninety percent of the A-locus mAb and only 80 percent of the B-locus mAb mapped to AlCo. The location of the mapped amino acids correlated with the quality of the mAb as typing reagent. The 226 mAb mapped to AlCo had higher combined correlation coefficients and inclusion values (r=0.73, Inc=0.88) than the 42 mAb with at least one residues located in the Gr (r=0.61, Inc=0.77). Examples of AlCo include the mAb for A*02 subtypes mapping Glycine at residue 62 (G62), monospecific A1 reagents (R163-A.D166-A.G167) and B8/B59 reactive mAb (F67-E45-T163). Examples of Gr-pEp included mAb for the B*40/27/47 groups (E163-L32-T24) and those differentially alleles with alleles of the A*68 group (e.g. A*02/A*6802/A*6901, H114-Y116-T142- H145). Epitopes defined by residues located in AlCo seem to be uniformly identified. In contrast, less consistent definition by mAb was observed for the groove-dependent epitopes which may arise from variations in the peptides bound by each allele.