Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope.
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 ovalbumin(323-339) ((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.
Hudson
Krystalyn E
KE
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Lin
Eugene
E
Hendrickson
Jeanne E
JE
Lukacher
Aron E
AE
Zimring
James C
JC
D019264:Adoptive Transfer; D000818:Animals; D001419:Bacteria / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D005434:Flow Cytometry; D016679:Genome, Viral / Q000235:genetics; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000235:genetics / Q000276:immunology*; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology
D001426:Bacterial Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007518:Isoantibodies; D010446:Peptide Fragments; D010047:Ovalbumin; C421864:hen egg lysozyme; D009113:Muramidase