Immunotolerance toward native αA-crystallin in knockout mice deficient in the functional protein

Puwat Charukamnoetkanok, James P. Brady, Eric F. Wawrousek, Charles E. Egwuagu, J. Samuel Zigler, Barbara P. Vistica, Scott M. Whitcup, Igal Gery

Research output: Contribution to journalArticle

Abstract

Immune response against self antigens is normally prevented by an elaborate immunotolerance mechanism. A potential problem for recipients of gene therapy is, therefore, an immune response against the newly introduced gene product. To examine this issue we tested the immune response to the native proteins in knockout (KO) mice in which the genes for αA- or αB-crystallin were disrupted by partial or complete gene deletion, respectively. αA- and αB-crystallins are two immunologically distinct polypeptides which form the large (∼800 kDa) complex in the lens referred to as α-crystallin. When immunized with murine α-crystallin, αB-crystallin KO mice, in which the corresponding gene was completely deleted, responded well to the absent self antigen. In contrast, αA-crystallin KO mice, with the partial gene deletion, resembled wild type (WT) mice in being immunotolerant toward the native crystallin. Although no functional αA-crystallin could be detected in the lens of αA-crystallin KO mice, mRNA transcript coding for a truncated αA-crystallin gene was found in thymi of these mice, suggesting that thymic expression of a residual fragment of the protein is responsible for the tolerance induction. These data suggest that nonfunctional proteins may induce immunotolerance and protect recipients of gene therapy from immunity against the native proteins.

Original languageEnglish (US)
Pages (from-to)259-265
Number of pages7
JournalImmunology Letters
Volume89
Issue number2-3
DOIs
StatePublished - Oct 31 2003

Keywords

  • Immunotolerance
  • Knockout mice
  • Lens crystallins
  • Self antigens
  • Thymic deletion

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Charukamnoetkanok, P., Brady, J. P., Wawrousek, E. F., Egwuagu, C. E., Zigler, J. S., Vistica, B. P., Whitcup, S. M., & Gery, I. (2003). Immunotolerance toward native αA-crystallin in knockout mice deficient in the functional protein. Immunology Letters, 89(2-3), 259-265. https://doi.org/10.1016/S0165-2478(03)00153-6