A 32-year-old man is diagnosed with human immunodeficiency virus (HIV) infection. His CD4 T-lymphocyte count is 450 cells/mm and his HIV RNA viral load is 45,000 copies/mL. The physician plans to initiate an antiretroviral therapy regimen that includes abacavir. Before prescribing this medication, the physician orders a genetic test to prevent a potentially fatal, immune-mediated hypersensitivity reaction. The specific host allele being tested for encodes a protein that is normally involved in which of the following cellular processes?
- Antigen presentation to T cellsAnswer
- BHepatic cytochrome P450 drug metabolism
- CViral co-receptor binding and cellular entry
- DGlucuronidation of lipophilic molecules
- ETransmembrane transport of organic anions
Answer
Antigen presentation to T cells
The patient is about to start abacavir, a nucleoside reverse transcriptase inhibitor (NRTI). Abacavir is strongly associated with a severe, potentially life-threatening hypersensitivity reaction in patients who carry the HLA-B*5701 allele. Therefore, pharmacogenomic screening for this allele is mandatory prior to drug initiation. The HLA-B gene encodes a major histocompatibility complex (MHC) class I molecule. In normal physiology, MHC class I molecules are present on the surface of all nucleated cells and are responsible for presenting endogenous antigens to CD8+ cytotoxic T cells. In susceptible individuals, abacavir binds non-covalently to the HLA-B*5701 protein, altering the presentation of self-peptides and triggering an inappropriate, systemic CD8+ T-cell response.
Step-by-Step Solution
Key Concept
Pharmacogenomic screening for the HLA-B*5701 allele is mandatory before starting abacavir; this allele encodes an MHC class I molecule involved in antigen presentation to T cells.