Figure 1.
Immunoediting in aAA through recurrent somatic loss of HLA class I. (A) Bar graph showing somatic HLA loss in patients with aAA compared with patients with PNH and healthy control patients. n, number of patients analyzed. *P < .05. Venn diagram shows the mechanism of HLA loss among 11 affected patients. (B) Schematic diagram showing the distribution of inactivating mutations in HLA class I alleles. α-1, α-2, and α-3 represent the α-1, α-2- and α-3 domains of HLA-A and HLA-B proteins; cp, connecting peptide. Frameshift mutations, black circles; nonsense mutations, open circles; mutated start codon, black square. (C) Bar graph showing the number of patients with mutations in a given HLA class I allele, with a corresponding pie chart plot depicting the clonal structure of HLA loss for each affected patient. The size of the pie slice corresponds to the size of each individual clone (percentage of total cells) as estimated from SNP-A analysis and percentage of mutant NGS reads. (D) A flowchart summarizing analyses performed in this manuscript.