HLA DRB115:01-DQB106:02-Restricted Human CD4+ T-Cells are Selectively Activated with Amoxicillin-Peptide Adducts

Posted by Adam Awdish on Dec 16, 2020

Pooled Human AB Serum Plasma Derived from Innovative Research was used in the following study:

HLA DRB1*15:01-DQB1*06:02-Restricted Human CD4+ T-Cells are Selectively Activated with Amoxicillin-Peptide Adducts

Arun Tailor, Xiaoli Meng, Kareena Adair, John Farrell, James C Waddington, Ann Daly, Munir Pirmohamed, Gordon Dear, B Kevin Park, Dean J Naisbitt

Toxicological Sciences
August 10, 2020

Idiosyncratic drug-induced liver injury (DILI) is a major health concern often associated with a high patient death rate. Amoxicillin-clavulanate is the most common cause of DILI, and the detection of drug-specific CD4+ T-cells in patients with DILI suggests it originates somewhere in the immune system. Researchers in this study aimed to (1) investigate whether amoxicillin-modified HLA-DRB1*15:01-DQB1*06:02 binding peptides selectively activate DILI patient T-cells and (2) define the nature of the T-cell response with respective to antigen structure.

The researchers were able to generate Amoxicillin-modified peptides and then purified and characterized them using mass spectrometry. Next, key fragment ions derived from the cleavage of the peptide backbone were identified for each modified peptide to distinguish positional derivatives and the amoxicillin peak. Researchers then analyzed each batch of peptides in order to quantify unbound amoxicillin. The amoxicillin-modified peptides were found to contain approximately 2-3% unbound amoxicillin, which is well below the concentration of amoxicillin that scientists have previously shown could activate T-cells (8µM).