DOI: 10.1097/TP.0b013e31819f6427
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Issn Print: 0041-1337
Publication Date: 2009/04/27
Structural Limitations to the Mimetic HLA Epitope Hypothesis
Nori Sasaki; Adam Idica; Paul I. Terasaki
Excerpt
In response to the letter of Kosmoliaptsis et al., we wish to clarify that the objective of our article (1) was to provide an explanation for the unexpected binding of monoclonal antibodies and extra antibodies produced in transplantation. Primary and mimetic epitopes, defined by three identical amino acids similardistances apart, may account for the “specificity” or “antigenic determinants” of the antibody binding. Nonpolymorphic positions and surrounding amino acids are excluded because they are not likely to define the specificity of reactivity. Our observations on mAb 2 support the idea that surrounding the amino acids do not have an effect on the specificity but rather the affinity of binding. mAb 2 is specific for HLA A*1102, A*1101, and A*4301. Note that the antibody binds to A*1102 and A*1101 with similar affinities as reflected by their MFI. Conversely, the same antibody binds A*4301 at approximately 50% of the MFI. A*1102 and A*1101 only differ in their amino acid sequence at a single position (position 19), whereas A*4301 has different amino acids at 18 positions when compared with A*1101 (2), suggesting that the amino acids adjacent to determinants do affect the “affinity” of the antibody binding. We concur with the letter that while defining affinities of the antibody, the hydrophobicity and electrostatic properties of the adjacent amino acids in the antibody binding “pocket” should be considered.
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