Deficient antigen processing of a protein quaternary structure can be overcome by receptor‐mediated uptake

Nathalie Rouas‐Freiss, Franck Housseau, Jean‐Michel ‐M Bidart, Christian Bonnerot, Sebastien Amigorena, Jean‐Gérard ‐G Guillet, Dominique Bellet

Research output: Contribution to journalArticlepeer-review

Abstract

Human chorionic gonadotropin (hCG) is a dimer of non‐covalently associated alpha (hCG‐α) and beta (hCG‐β) subunits. This molecule was used to study whether receptor‐mediated uptake influences the presentation of a protein quaternary structure. Unprimed splenocytes and a B cell lymphoma were capable of presenting only the free (hCG‐α) but not the combined (hCG) α subunit to hCG‐α T cell hybridomas, while hCG‐α‐primed lymph node cells (LNC) responded to both hCG‐α and hCG. As antigen (Ag)‐specific antigen‐presenting cells (APC) present in the hCG‐α‐primed LNC population may be potentially effective for presenting hCG, we investigated the role of specific Ag capture, through mIg and FcγR, in the processing and presentation of hCG and hCG‐a to HAG 5, a T cell hybridoma directed against the immunodominant region (amino acids 61‐81) of hCG‐α. Results showed that only B cells bearing membrane immunoglobulin capable of recognizing hCG‐α and hCG, and present in hCG‐α‐primed mice, were extremely effective in presenting the free as well as the combined a subunit. The effect of FcR‐mediated uptake was analyzed using a B cell line transfected with the FcγRII‐B2 gene to present immune complexes of either hCG‐α or hCG. We found that hCG‐α and hCG were presented equally well, whatever the Ag‐binding site of each antibody to hCG or its a subunit. Using HBG 6, an hCG‐β Tcell hybridoma, we performed similar experiments with the FcγRII‐B2 cell line and determined that the potentiation of hCG presentation to HBG 6 was similar to that observed with HAG 5. Then kinetic experiments were performed to examine the effect of Ag uptake through FcR on processing. Results demonstrated that the uptake pathway drastically influenced the expression of α T cell determinants in the αβ dimer. In addition, treatment with cycloheximide, a protein synthesis inhibitor, only impaired the ability of APC to present specifically captured Ag. Thus, the processing pathway for specifically captured Ag might be different from the pathway used to process nonspecifically captured Ag. This observation might explain why receptor‐enhanced uptake bypasses the inefficient processing of the hCG quaternary structure and enables similar efficiency in the presentation of α and β T cell specificities. These findings provide new insight into the antigenicity of oligomeric molecules, which is modified whether antigen capture is specific or not.

Original languageEnglish (US)
Pages (from-to)3335-3344
Number of pages10
JournalEuropean Journal of Immunology
Volume23
Issue number12
DOIs
StatePublished - Dec 1993
Externally publishedYes

Keywords

  • Antigen processing
  • Antigen‐presenting cell
  • Protein quaternary structure
  • Receptor‐mediated uptake
  • T cell

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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