Determination of DC-SIGN and DC-SIGNR Repeat Region Variations

DC-SIGN and DC-SIGNR efficiently bind HIV-1 and other viral as well as nonviral pathogens and assist either cis or trans infection. Both are type II transmembrane proteins that consist of an N-terminal cytoplasmic domain, a repeat region consisting of seven 23-amino-acid tandem repeats, and a C-terminal C-type carbohydrate recognition domain that binds mannose-enriched carbohydrate modifications of host and pathogen proteins. The normal functions of DC-SIGN and DC-SIGNR include binding to ICAM-2 and ICAM-3. Binding of DC-SIGN to ICAM-2 on endothelial cells facilitates chemokine-induced dendritic cell extravasation; binding to ICAM-3 on T lymphocytes provides the initial step for establishing cell-mediated immunity. Based on the number of tandem repeats, DC-SIGNR is highly polymorphic in the repeat region, while variations in DC-SIGN repeat region are rare. A change in the number of DC-SIGN and DC-SIGNR repeats may influence their normal functions as well as their binding capacity to viral and nonviral pathogens. This chapter describes the methods for detection of DC-SIGN and DC-SIGNR repeat region variations by polymerase chain reaction.