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.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Antigen‐presenting cells
- Major histocompatibility complex down‐regulation
- Monoclonal antibody fragments