1  Functional Divergence

Heterozygosity of HLA class I genes is associated with better outcomes after HIV infection. This is thought to be due to a greater repertoire of HIV peptides presented and cytotoxic T cell response. However, looking at HLA class I allotype alone does not take into account differences in actual peptide repertoire. Viard et al. (2024) developed a metric to measure this difference, termed “functional divergence.” Functional divergence predicts the peptide repertoire as a continuum. They showed that greater functional divergence was associated with better HIV outcomes. Functional divergence may be relevant to other diseases where HLA heterozygosity confers advantage, such as infection, vaccination, and immunotherapy.

You can download functional divergence estimates for pairwise combinations of HLA-A, HLA-B, and HLA-C alleles from their article’s Supplementary Materials. The functional divergence measure ranges from 0 (i.e., smallest functional divergence) to 1 (i.e., greatest functional divergence).

Viard, Mathias, Colm O’hUigin, Yuko Yuki, Arman A. Bashirova, David R. Collins, Jonathan M. Urbach, Steven Wolinsky, et al. 2024. “Impact of HLA Class I Functional Divergence on HIV Control.” Science 383 (6680): 319–25. https://doi.org/10.1126/science.adk0777.