Down‐regulation of class II major histocompatibility complex molecules on antigen‐presenting cells by antibody fragments

Damir Vidović, Fiorenza Falcioni, Botond Siklodi, Charles J. Belunis, David R. Bolin, Kouichi Ito, Zoltan A. Nagy

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Certain HLA class II‐specific monoclonal antibodies (mAb) cause up to 90% decrease in the cell surface expression of class II molecules. This down‐regulation is isotype‐specific, i.e. DR‐specific mAb do not affect the expression of DP and DQ molecules. However, antibodies binding to one DR allotype down‐regulate both allotypes in heterozygous antigen‐presenting cells (APC), indicating that the phenomenon is not a direct consequence of ligation. All down‐regulating mAb identified recognize the first (peptide binding) domains of class II heterodimers, and strongly inhibit the activation of class II‐restricted human T cells in vitro. Conversely, non‐down‐regulating mAb fail to inhibit T cell activation, and most of them (four out of five) recognize class II second domains. Down‐regulating antibodies are cytotoxic for B lymphoblastoid cell lines and for a small proportion of normal activated B cells. Their F(ab′)2 fragments mediate both down‐regulation and cytotoxicity, whereas the monovalent Fab fragments are not cytotoxic, but retain the down‐regulatory and T cell inhibitory properties. These findings raise the possibility of a class II major histocompatibility complex‐specific, antibody‐based immunosuppressive therapy without cytotoxic side effects.

Original languageEnglish (US)
Pages (from-to)3349-3355
Number of pages7
JournalEuropean Journal of Immunology
Volume25
Issue number12
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • Antigen‐presenting cells
  • Major histocompatibility complex down‐regulation
  • Monoclonal antibody fragments

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