Allele-specific peptide presentation of human leukocyte antigens: implications for tumor immunotherapy

Human leukocyte antigen (HLA) class I plays a central role in the immune defense against microbes and tumors by presenting endogenously processed peptides to T-cells. Few studies have addressed the question as to what extent variants of the same allelic HLA group differ in their peptide motif.

To answer this question for the HLA-A*66 family, which is a sub-group of the widespread serological HLA-A10 group, peptides eluted from recombinant A*6602 and A*6603 molecules were sequenced and have with data previously reported for A*6601.

The amino acid exchange between A*6602 and A*6603 (Gln70His) has no impact on the peptide motif. By contrast, the amino acid exchange Arg163Glu that distinguishes A*6601 from A*6602/6603 results in a change of the peptides preferentially bound.

Minor amino acid differences between HLA molecules may have a large impact on peptide presentation. For immunotherapy based on tumor-related peptides, it is crucial that the tumor specific peptide is presented by the patients' HLA molecules. For this reason, patients need to be typed not only at the HLA group level, but also at the allelic level.