Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope

Author:

Hudson Krystalyn E.1,Lin Eugene1,Hendrickson Jeanne E.12,Lukacher Aron E.1,Zimring James C.1

Affiliation:

1. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA; and

2. AFLAC Cancer Center and Blood Disorders Service, Children's Healthcare of Atlanta, Division of Pediatric Hematology/Oncology, Emory University School of Medicine, GA

Abstract

Abstract Humoral alloimmunization to red blood cell (RBC) antigens is a clinically significant problem that can lead to transfusion reactions and difficulty in locating future compatible blood for transfusion. However, factors regulating responder/nonresponder status are only partially understood. Herein, we identify a series of microbes with 100% identity in 8– to 9–amino acid peptides containing the variant amino acids in Kell, Kidd, and Duffy antigens. To test the hypothesis that infection with such a microbe could predispose to RBC alloimmunization, a mouse model was developed using murine polyoma virus expressing a defined CD4+ T-cell epitope ovalbumin323-339 ((OVA)323-339) and subsequent transfusion with RBCs expressing a B-cell epitope (hen egg lysozyme [HEL]) fused to (OVA)323-339. Whereas infection alone induced no detectable anti-HEL, subsequent RBC transfusion induced 100- to 1000-fold more anti-HEL in mice that had been previously infected compared with control mice. This effect did not occur with wild-type polyoma virus or RBCs expressing HEL alone. Together, these data indicate that prior exposure to a pathogen with small peptide homology to RBC antigens can lead to an enhanced primary alloantibody response. As such priming is not detectable by current clinical tests, it is unknown to what extent this occurs in human alloimmunization.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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