A precise characterisation of peptide binding stability to HLA-C alleles and correlation with the progression of HIV-1 infection and HIV-1 related neurocognitive impairment

This study investigates how the molecular binding stability of the HLA-C/β2-microglobulin/peptide complex influences HIV-1 progression and associated neurocognitive impairment. Using the NetMHCpan4.1 tool to predict binding affinity, a quantitative stability score was determined by calculating the area under the curve (AUC) for the most common human HLA-C allotypes. Clinical correlation in naïve HIV-1 infected subjects revealed that alleles such as C*05:01 and C*08:02 are the most stable, while C*07:04, C*07:01, and C*08:01 are the least stable. The results show that individuals with slower progression to AIDS and those without neurocognitive impairment exhibit significantly higher HLA-C stability scores compared to rapid progressors (P = 0.0113) and patients with cognitive deficits (P = 0.0074). These findings demonstrate that AUC-based stability analysis provides a superior method for classification compared to previous binary models, highlighting the prognostic value of HLA-C stability and its potential as a therapeutic target in HIV-1 infection.