Influence of HLA-DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model

Y. H. Sheen, G. Rajagopalan, C. M. Snapper, Hirohito Kita, C. I. Wi, P. J. Umaretiya, Young J Juhn

Research output: Contribution to journalArticle

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Abstract

Asthma is independently associated with HLA-DR3 and increased risks of pneumococcal diseases. We aimed to determine whether HLA-DR polymorphism (HLA-DRB1*03), sensitization to house dust mite (HDM), or their interaction affects humoral immune responses to pneumococcal polysaccharide and protein antigens of intact pneumococci. Induction of serum titers of anti-pneumococcal polysaccharide and anti-surface protein IgM and IgG in response to immunization with intact pneumococci (Pn) serotype 14 was determined using humanized HLA-DR3 and DR2 transgenic mice. Transgenic mice were sensitized by injecting HDM and challenged with intranasal HDM. Mice were subsequently immunized with heat-killed Pn14 at day 24. Serum titers of anti-phosphorylcholine (PC) IgM and IgG, anti-pneumococcal polysaccharide, capsular type 14 (PPS14) IgM and IgG, and anti-pneumococcal surface protein A (PspA) IgG were measured. We included a total of 44 mice (22 DR3 and 22 DR2 mice) and half of mice in each group were sensitized with HDM (i.e. 22 HDM-sensitized and 22 control mice). HDM-sensitized mice, irrespective of HLA-DR polymorphism, had significantly lower humoral immune responses. HLA-DR3 mice, irrespective of HDM sensitization, elicited a significantly lower anti-PC IgG response. In contrast, the anti-PspA IgG response was higher in DR3 relative to DR2 mice. The effect of HDM sensitization on lowering humoral immune responses to Pn14 was observed in DR3 mice regardless of the nature of the antigen, whereas such decreases were observed only for the anti-PPS14 IgG and anti-PC IgM responses in DR2 mice. HDM sensitization lowered humoral immune responses to intact pneumococcus and this effect was significantly modified by the HLA-DR polymorphism.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalHLA
Volume88
Issue number1-2
DOIs
StatePublished - Jul 1 2016

Fingerprint

Pyroglyphidae
HLA-DR Antigens
Humoral Immunity
Streptococcus pneumoniae
Transgenic Mice
HLA-DR3 Antigen
Phosphorylcholine
Immunoglobulin G
Polysaccharides
HLA-DR2 Antigen
Antigens
HLA-DRB1 Chains
Serum
Immunoglobulin M
Immunization
Membrane Proteins
Asthma
Hot Temperature

Keywords

  • Adaptive immunity
  • HLA-DR3
  • Sensitization
  • Streptococcus pneumoniae
  • Transgenic mice

ASJC Scopus subject areas

  • Genetics
  • Immunology
  • Immunology and Allergy

Cite this

Influence of HLA-DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model. / Sheen, Y. H.; Rajagopalan, G.; Snapper, C. M.; Kita, Hirohito; Wi, C. I.; Umaretiya, P. J.; Juhn, Young J.

In: HLA, Vol. 88, No. 1-2, 01.07.2016, p. 25-34.

Research output: Contribution to journalArticle

Sheen, Y. H. ; Rajagopalan, G. ; Snapper, C. M. ; Kita, Hirohito ; Wi, C. I. ; Umaretiya, P. J. ; Juhn, Young J. / Influence of HLA-DR polymorphism and allergic sensitization on humoral immune responses to intact pneumococcus in a transgenic mouse model. In: HLA. 2016 ; Vol. 88, No. 1-2. pp. 25-34.
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