Adaptive immune response to model antigens is impaired in murine leukocyte-adhesion deficiency-1 revealing elevated activation thresholds in vivo

Thorsten Peters, Wilhelm Bloch, Oliver Pabst, Claudia Wickenhauser, Claudia Uthoff-Hachenberg, Susanne V Schmidt, Georg Varga, Stephan Grabbe, Daniel Kess, Tsvetelina Oreshkova, Anca Sindrilaru, Klaus Addicks, Reinhold Förster, Werner Müller, Karin Scharffetter-Kochanek

Publication: Contribution to journalJournal articlesResearch

Abstract

Absence of β₂ integrins (CD11/CD18) leads to leukocyte-adhesion deficiency-1 (LAD1), a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β₂ integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β₂ integrin-deficiency (CD18⁻/⁻). CD18⁻/⁻ mice generated only weak IgG responses after immunization with tetanus toxoid (TT). In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl)₂₁ acetyl chicken γ globulin (NP₂₁-CG), even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18⁻/⁻ mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18⁻/⁻ mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT) efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.

Original languageEnglish
JournalClinical & developmental immunology
Volume2012
DOIs
Publication statusPublished - 01.01.2012

Research areas and keywords

  • Adaptive Immunity
  • Animals
  • Antigens, CD18
  • Cell Adhesion
  • Disease Models, Animal
  • Haptens
  • Humans
  • Immunization
  • Immunoglobulin G
  • Leukocyte-Adhesion Deficiency Syndrome
  • Lymphocyte Activation
  • Mice
  • Mice, Knockout
  • Protein Engineering
  • T-Lymphocytes
  • Tetanus Toxoid

Fingerprint

Dive into the research topics of 'Adaptive immune response to model antigens is impaired in murine leukocyte-adhesion deficiency-1 revealing elevated activation thresholds in vivo'. Together they form a unique fingerprint.

Citation