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What is 4-field resolution HLA typing?

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HLA typing resolution refers to the level of detail to which the HLA alleles are identified. There are 4 possible fields of resolution:

  1. Antigen recognition site (1-field) — Identifies the major antigen recognition site variants, e.g. HLA-A*02
  2. Protein specificity (2-field) — Identifies all encoding variations within the antigen recognition site, e.g. HLA-A*02:01
  3. Allelic specificity (3-field) — Identifies the specific protein sequence encoded, including synonymous codon variations, e.g. HLA-A*02:01:01
  4. Full gene sequence (4-field) — Identifies the specific intron and UTR variants for an allele, e.g. HLA-A*02:01:01:01

4-field resolution allows matching based on the full protein sequence.

The HLA genes play a critical role in the immune system by encoding cell surface proteins that present antigen peptides to T cells. Matching HLA types between organ donors and transplant recipients is important for transplant success.

4-field resolution is widely considered high resolution HLA typing in transplantation and disease association studies. It provides key information for donor selection and epitope matching. However, non-coding genomic variation can also impact HLA expression and function. 6-digit resolution captures this.

In summary, 4-field HLA typing identifies HLA allele variants at a clinically actionable level of resolution for many applications. However, increasing use of higher resolution NGS-based HLA typing continues to reveal additional variation that may provide further transplant and immunogenetic insights.