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

Krystalyn E. Hudson, Eugene Lin, Jeanne E. Hendrickson, Aron E. Lukacher, James C. Zimring

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3989-3996
Number of pages8
JournalBlood
Volume115
Issue number19
DOIs
StatePublished - May 13 2010

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Isoantibodies
T-Lymphocyte Epitopes
Blood
Polyomavirus
Erythrocytes
Antigens
Viruses
B-Lymphocyte Epitopes
Amino Acids
Erythrocyte Transfusion
Peptides
Infection
Blood Transfusion
Pathogens
Cells
hen egg lysozyme

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Hudson, Krystalyn E. ; Lin, Eugene ; Hendrickson, Jeanne E. ; Lukacher, Aron E. ; Zimring, James C. / Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope. In: Blood. 2010 ; Vol. 115, No. 19. pp. 3989-3996.
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Regulation of primary alloantibody response through antecedent exposure to a microbial T-cell epitope. / Hudson, Krystalyn E.; Lin, Eugene; Hendrickson, Jeanne E.; Lukacher, Aron E.; Zimring, James C.

In: Blood, Vol. 115, No. 19, 13.05.2010, p. 3989-3996.

Research output: Contribution to journalArticle

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