Differential Alloreactivity: Lessons Learned From a Singular
                    HLA
                    Locus

Esteban Arrieta‐Bolaños

doi:10.1111/tan.70489

journal article Open Access Dec 01, 2025

Differential Alloreactivity: Lessons Learned From a Singular HLA Locus

Esteban Arrieta‐Bolaños

HLA Vol. 106 No. 6 · Wiley

View at Publisher Save 10.1111/tan.70489

Abstract

ABSTRACT
Alloreactivity entails the recognition of cells and tissues from one individual as foreign by T cells and other immune effectors from another individual. Alloreactive immune responses play an important role in various clinical contexts, in particular in transplantation. Major drivers of these responses are the highly immunogenic, non‐self HLA molecules. However, the immunogenicity of these allogeneic HLA molecules has been observed to vary according to certain immunobiological and immunogenetic parameters, leading to the concept of differential alloreactivity. Recent progress in unveiling the underpinnings of this phenomenon has been made for the frequently mismatched HLA‐DP allotypes, whose singular genomic, structural and population genetics characteristics offer an ideal scenario for these investigations. Studies in the HLA‐DP context have highlighted the immunopeptidome overlap between self and non‐self HLA allotypes, as well as its editing by non‐classical class II chaperones HLA‐DM and HLA‐DO, as a main determinant of their immunogenicity likely via indirect effects of thymic education. Recent evidence suggests that these observations could also be extended to alloresponses directed against HLA molecules encoded by other loci. How these functional characteristics of HLA molecules shape allorecognition by T‐cell subsets, and how they translate into different clinical consequences in the context of transplantation will be the subject of the present review.

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Details

Published: Dec 01, 2025
Vol/Issue: 106(6)
License: View

Authors

E

Esteban Arrieta‐Bolaños

Institute for Experimental Cellular Therapy, University Hospital Essen Essen Germany

Cite This Article

Esteban Arrieta‐Bolaños (2025). Differential Alloreactivity: Lessons Learned From a Singular HLA Locus. HLA, 106(6). https://doi.org/10.1111/tan.70489

Differential Alloreactivity: Lessons Learned From a Singular HLA Locus

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