HLA-DQ restricted activation of nitroso- sulfamethoxazole-specific CD4+ T-lymphocytes

Background Sulfamethoxazole hypersensitivity has been used as a paradigm to study the role of drug metabolism in the activation of T-cells. CD4+ T-cells isolated from blood/ skin of 100% of hypersensitive patients are activated with the protein-reactive metabolite nitroso sulfamethoxazole (SMX.NO). Since SMX.NO binds to multiple cellular proteins it is assumed that peptides derived from the modified protein interact with a number of diverse HLA molecules to activate T-cells; however, the HLA molecules that interact with SMX-NO modified peptides has not been studied. Method The aims of this study were to examine the HLA molecules that present SMX.NO (derived peptides) to T-cells and determine the extent of alloreactivity. T-cell clones were generated from 4 hypersensitive patients with cystic fibrosis. Drug-specific proliferative responses and cytokine secretion were measured using [3H]-thymidine incorporation and ELISpot, respectively. Anti-human class I and class II (DR, DP, and DQ) antibodies were used to determine HLA restriction. Antigen presenting cells expressing different HLAs were used to define the alleles involved in the presentation of SMX.NO-derived antigens to T-cells. Results