The immunopeptidome guides permissive HLA mismatch

In this issue of Blood, Meurer et al(1) report on the mechanistic underpinning of permissive HLA-DPB1 mismatch using mass spectrometry-based analysis of the HLA-DP immunopeptidome, T-cell receptor beta (TCR beta) clonotype sequencing, and exploration of HLA-DM-mediated peptide editing. Permissive HLA-DPB1 mismatches show greater overlap in their HLA-presented peptide repertoire compared with their nonpermissive counterparts. This results in both a lower frequency and diversity of alloreactive TCRb clonotypes (see figure), which could be reversed by silencing of the peptide editor HLA-DM.

Automated summary

Permissive HLA-DPB1 mismatches have more overlap in HLA-presented peptide repertoire, leading to lower frequency and diversity of alloreactive TCRb clonotypes, which can be reversed by silencing of the peptide editor HLA-DM.