Background. Knowledge of the human leukocyte antigen (HLA) amino acid (AA) sequence combined with crystallographic structural data may enable prediction of the relative immunogenicity of individual donor/recipient HLA mismatches. Methods. Multiple sera from 32 highly sensitized patients awaiting kidney transplantation were screened using Luminex/single-antigen beads to determine the HLA-specific antibody levels against mismatched HLA class I specificities. A computer program was developed to allow intralocus and interlocus comparison of mismatched HLA-A and -B specificities with corresponding recipient HLA class I type, and to determine the number, position, and physiochemical disparity (hydrophobicity and electrostatic charge) of polymorphic AA. Results. HLA-specific antibody was detected against 1666 (85%) of the 1964 mismatched HLA specificities evaluated, with a close correlation between increasing number of AA polymorphisms and the presence and magnitude of the alloantibody response (P10,000). Conclusion. Differences in AA number, hydrophobicity, and electrostatic charge between HLA class I specificities enable prediction of donor HLA class I types with low immunogenicity for a given recipient.
- HLA immunogenicity
- Electrostatic charge