ArticlebioRxiv : the preprint server for biology2026
COMBO-RATE: An experimentally validated bioinformatic tool to identify promiscuous HLA restrictions.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
Defining HLA restriction of T cell epitopes is essential for understanding immune responses in infectious disease, autoimmunity, and vaccine design. Current bioinformatic programs, including the IEDB RATE tool, enable inference of single-HLA restrictions from immune response data of HLA-typed donors. However, T cell epitopes are frequently presented by multiple HLA alleles, a phenomenon termed promiscuous restriction, limiting the utility of single-allele approaches. To address this limitation, we developed COMBO-RATE, an extension of RATE that systematically evaluates combinations of HLA alleles to identify multi-allelic restriction patterns. Analysis of three independent datasets spanning distinct antigen systems and different epitope discovery strategies revealed that promiscuous restriction is a near-universal feature of immunodominant epitopes. Focusing on the 43 immunodominant CD4
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