What type of study is this?

This is a In Vitro Study study.

What question did this study set out to answer?

To explore the relationship between HLA-DRB1 variants and T cell responses in Staphylococcus aureus bacteremia risk.

January 14, 2026Open Access

P-1559. Investigating the Effect of HLA-DRB1 Variants on T cell Response as a Contributing Risk Factor for Staphylococcus aureus Bacteremia

Key Points

To explore the relationship between HLA-DRB1 variants and T cell responses in Staphylococcus aureus bacteremia risk.
Measured CD4+ T cell responses to HLA-DRB1 variants using flow cytometry.
Isolated CD4 T cells from healthy donors and co-cultured with B-lymphoblastoid cell lines.
Assessed cytokine production after exposure to Staphylococcus aureus at different multiplicity of infection levels.
Variable T cell responses observed across different HLA-DRB1 alleles.
HLA-DRB1*07:01 showed significantly higher T cell activation compared to other variants.
Cytokine responses varied significantly, indicating distinct immune responses to S. aureus.

Abstract

Abstract Background The impact of host genetic variability on Staphylococcus aureus bacteremia (SAB) risk is unknown. In genome-wide association studies, we identified specific HLA-class II variants associated with higher risk (HLA-DRB1*04:01 OR = 1.121 (0.952, 1.321) MOI 5= 6.65 ±3.6; MOI 50= 7.96 ±4.1) compared to HLA-DRB1*04:01 (MOI 0.5= 1.48 ±0.27; MOI 5= 3.15 ±0.77; MOI 50= 4.96 ±1.7) or 03:01 (MOI 0.5 =1.95 ±0.66; MOI 5= 2.56 ±0.81; MOI 50= 2.42 ±0.86) across S. aureus concentrations. Variable CD4 T cell cytokine response to recognition of S. aureus peptide was also observed across HLA-DRB1*04:01, 03:01, and 07:01 variants. Cytokines associated with Th1 response and T cell proliferation are shown, but these markers did not reach statistical significance. Conclusion We provide in vitro evidence to suggest that HLA-DRB1 variation in S. aureus peptide presentation impacts CD4+ T cell activation and may explain the association between certain HLA-DRB1 haplotypes and SAB. Disclosures Vance G. Fowler, MD, MHS, Affinergy, Janssen, Contrafect: Advisor/Consultant|AstraZeneca; EDE; Basilea: Grant/Research Support|Debiopharm, GSK; Affinium, Basilea,: Advisor/Consultant|Destiny, Amphliphi, Armata, Akagera: Advisor/Consultant|Merck; Contrafect; Karius; Janssen: Grant/Research Support|UpToDate: Royalties|Valanbio: Stock options

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