Boosting immune response with the invariant chain segments via association with non-peptide binding region of major histocompatibility complex class II molecules

BMC Immunology

Weiyi Yu¹  Xuelan Liu¹  Fazhi Xu¹  Ling Pan¹  Fantao Meng¹  Fangfang Chen¹ 

[1] Key Laboratory of Zoonoses of Anhui Province, Anhui Agricultural University, 130 Changjiang West Road, Hefei 230036, China

关键词: Membrane co-localization;    Antibody;    MHC II;    Hybrid;    Epitope;    Li-segments;   

Others  :  1077873
DOI  :  10.1186/1471-2172-13-55

 received in 2012-03-29, accepted in 2012-09-17,  发布年份 2012

【 摘 要 】

Background

Based on binding of invariant chain (Ii) to major histocompatibility complex (MHC) class II molecules to form complexes, Ii-segment hybrids, Ii-key structure linking an epitope, or Ii class II-associated invariant chain peptide (CLIP) replaced with an epitope were used to increase immune response. It is currently unknown whether the Ii-segment cytosolic and transmembrane domains bind to the MHC non-peptide binding region (PBR) and consequently influence immune response. To investigate the potential role of Ii-segments in the immune response via MHC II/peptide complexes, a few hybrids containing Ii-segments and a multiepitope (F306) from Newcastle disease virus fusion protein (F) were constructed, and their binding effects on MHC II molecules and specific antibody production were compared using confocal microscopy, immunoprecipitation, western blotting and animal experiments.

Results

One of the Ii-segment/F306 hybrids, containing ND (Asn–Asp) outside the F306 in the Ii-key structure(Ii-key/F306/ND), neither co-localized with MHC II molecules on plasma membrane nor bound to MHC II molecules to form complexes. However, stimulation of mice with the structure produced 4-fold higher antibody titers compared with F306 alone. The two other Ii-segment/F306 hybrids, in which the transmembrane and cytosolic domains of Ii were linked to this structure (Cyt/TM/Ii-key/F306/ND), partially co-localized on plasma membrane with MHC class II molecules and weakly bound MHC II molecules to form complexes. They induced mice to produce approximately 9-fold higher antibody titers compared with F306 alone. Furthermore, an Ii/F306 hybrid (F306 substituting CLIP) co-localized well with MHC II molecules on the membrane to form complexes, although it increased antibody titer about 3-fold relative to F306 alone.

Conclusions

These results suggest that Ii-segments improve specific immune response by binding to the non-PBR on MHC class II molecules and enabling membrane co-localization with MHC II molecules, resulting in the formation of relatively stable MHC II/peptide complexes on the plasma membrane, and signal transduction.

【 授权许可】

   
2012 Chen et al.; licensee BioMed Central Ltd.

【 图 表 】

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