Selective HLA restriction enables the evaluation and interpretation of immunogenic breadth at comparable levels to that observed with broader HLA distribution.

Jonathan Hare,Andrew Fiore‐Gartland,Morten Nielsen,Eric Hunter,Jill Gilmour,Edward Mcgowan

doi:10.1002/pmic.202100121

Abstract

Existing approaches to identifying predictive T-cell epitopes have traditionally utilized either 2-digit HLA super-families or more commonly utilizing autologous HLA alleles to facilitate the predictions. However, the use of these criteria may not consider the HLA representation within any target population. Here we propose a modification to concept of utilizing autologous HLA whereby subsets of individuals are selected for their specific HLA allele profiles and the representation they provide within a given population. Using this selective approach to HLA selection and the linkages to specific individuals may enable the design of more targeted experimentalstrategies.

Highlights

The use of in silico predictive algorithms to identify potential CD8 Tcell epitopes has expanded dramatically in recent years as the number and accuracy of the predictive models increases [1]
We propose a modification to concept of utilizing autologous human leukocyte antigen (HLA) whereby subsets of individuals are selected for their specific HLA allele profiles and the representation they provide within a given population
The traditional approach to utilizing these predictive algorithms has been to include autologous or population major histocompatability complex (MHC) Class I haplotypes as a precaution to ensure full HLA coverage

Summary

INTRODUCTION

The use of in silico predictive algorithms to identify potential CD8 Tcell epitopes has expanded dramatically in recent years as the number and accuracy of the predictive models increases [1]. The traditional approach to utilizing these predictive algorithms has been to include autologous or population MHC Class I haplotypes as a precaution to ensure full HLA coverage. This is predicated on two complimentary assumptions that: 1. 2. Immunogenic “breadth” can be empirically assessed as the cumulative number of immunogenic output, where the larger the metric the greater the “breadth” [7]. Immunogenic “breadth” can be empirically assessed as the cumulative number of immunogenic output, where the larger the metric the greater the “breadth” [7] In this viewpoint we aim to challenge both assumptions: Abbreviations: HLA, human leukocyte antigen; MHC, major histocompatability complex.

Restricted sub-populations represent the HLA diversity of larger cohorts

Findings

"Significance Statement"