Why can the same infection trigger different immune responses in different people?

Part of the answer lies in our human leukocyte antigen (HLA) genes. Understanding their diversity can help researchers design vaccines that account for the genetic backgrounds of the populations they are intended to protect.

HLA genes encode proteins that display small fragments of pathogens to immune cells, helping the body recognise and respond to infection. However, despite their extensive genetic diversity, African populations remain underrepresented in high-resolution HLA datasets. This leaves important gaps in the information available to guide immunological research and T-cell vaccine development.

In a GenDx webinar presented on 9 September 2026, Dr Tiza Ng’uni and Dr Nitalia Naidoo from the Africa Health Research Institute (AHRI) shared how the Ndhlovu Lab is addressing these gaps. Their presentation brought together two published studies: an analysis of HLA class I diversity across Eastern and Southern Africa and the discovery of a previously unreported allele, HLA-E*01:152.

Mapping African HLA diversity: what did the study find?

Dr Tiza Ng’uni

Research Associate and Project Manager

Dr Nitalia Naidoo

Postdoctoral Research Fellow and HLA Typing Lead

 

The first study, by Banjoko et al., published in Scientific Reports in 2025, analysed HLA-A, HLA-B and HLA-C data from 2,718 unrelated African participants drawn from HIV research cohorts in Kenya, Rwanda, Uganda, South Africa and Zambia. The researchers also compared these profiles with African American and European American datasets.

The team examined individual HLA variants, known as alleles, and combinations of alleles inherited on the same chromosome, known as haplotypes. Their analyses revealed substantial diversity within and between the sampled African populations. An allele that was common in one population could be much less frequent in another. For example, HLA-A*02:01 had an allele frequency of approximately 25% in the European American dataset, compared with 5.1% in the South African dataset.

Importantly, although African American HLA profiles were generally more similar to the African datasets than European American profiles were, they did not fully represent the diversity observed in the African populations studied. The message was clear: HLA data from one population cannot simply be assumed to represent another, even when there is shared ancestry.

A new HLA-E allele: what did high-resolution sequencing reveal?

Alongside the population analysis, the webinar highlighted the laboratory’s sequencing workflow. The team combined GenDx NGSgo-MX11-3 amplification of classical HLA loci with NGSgo-AmpX v2 amplification of HLA-E, followed by NGSgo Library Full Kit preparation, sequencing on the Illumina NextSeq 2000, and analysis using NGSengine. This approach enabled the detection of a sequence that did not match an existing HLA-E reference allele.

The resulting communication, by Naidoo et al., published in HLA in 2025, described HLA-E*01:152 in 12 individuals across four countries: six in Zimbabwe, four in South Africa, one in Zambia and one in Kenya. The allele differs from its reference sequence by a single DNA change that replaces lysine with arginine at amino acid position 174.

The published analysis also identified a strong association between HLA-E*01:152 and HLA-A*29:11, suggesting possible co-inheritance and raising questions for further investigation. The new allele was officially named by the WHO Nomenclature Committee for Factors of the HLA System in January 2025, and its sequence was deposited in GenBank.

Why is this important?

Together, these studies highlight three opportunities:

  • Informing vaccine design: Population-specific HLA data can help guide T-cell vaccine research towards broader coverage of the genetic diversity found in the intended populations.
  • Investigating immune function: Newly identified HLA-E variants provide opportunities to explore differences in peptide presentation, cell-surface expression and recognition by natural killer cells and CD8+ T cells. These remain questions to be tested, rather than established effects of HLA-E*01:152.
  • Strengthening reference datasets: Expanding African HLA datasets can reveal variation that is missed when research relies on data from other populations.

 

What comes next?

  • Larger studies involving more African populations, together with expanded analysis of HLA class II and non-classical HLA genes, will help build a more complete picture of this diversity. The webinar also highlighted capacity building, skills transfer and the development of shared HLA data resources as part of the programme’s wider direction.
  • For HLA-E*01:152, structural modelling and functional studies are needed to determine whether the amino acid substitution affects immune recognition or disease-related responses. Identifying the allele is an important first step; understanding what it does is the next.

To design vaccines with broad immune coverage, we must understand the HLA diversity of the people they are intended to protect.

Interested to find out more?

  • Explore Dr Tiza Ng’uni and Dr Nitalia Naidoo’s GenDx webinar, Mapping African HLA Diversity: High-Resolution Genotyping and Discovery of HLA-E*01:152: (Webinar Page)
  • Read the full Scientific Reports article, High resolution class I HLA-A, -B, and -C diversity in Eastern and Southern African populations: https://www.nature.com/articles/s41598-025-06704-4
  • Read the HLA communication, The Novel HLA-E*01:152 Allele Identified in African Populations Using Next-Generation Sequencing: https://onlinelibrary.wiley.com/doi/10.1111/tan.70247