Expanded Allelic Diversity of Non-Classical HLA Class I and MIC Loci Identified Using Full-Gene Hybrid Capture-Based...

Non-classical HLA Class I genes (HLA-E, -F, -G, -H) and MHC-related genes (MICA, MICB) regulate NK cell function and immune tolerance, yet their allelic diversity remains underexplored. Using capture-enriched full-gene sequencing of 943 healthy US transplant donors, we identified 26 novel alleles across HLA-E (2), HLA-F (6), HLA-G (4), HLA-H (5), MICA (3), and MICB (6). Each novel allele was identified in a single individual and differs from its closest known allele by a single-nucleotide polymorphism within the coding region. In addition, we confirmed the recently described allele HLA-G*01:01:33 in 16 unrelated donors. In all cases, it consistently co-segregated with HLA-A*34:01:01, HLA-F*01:01:01 and HLA-H*02:27, supporting the presence of a conserved haplotype. These findings expand the catalogue of non-classical HLA and MIC alleles, highlighting capture-enriched full-gene sequencing as a powerful tool for comprehensive immunogenetic profiling.