T Cell Receptor 'Clonotypes' Key to HIV-1 Infection Control

Distinct clonotypes seen for controllers, progressors; differ in their ability to inhibit viral replication

WEDNESDAY, June 13 (HealthDay News) -- The association of particular human leukocyte antigens (HLAs) with the ability of some individuals to control HIV-1 infection is modulated by clones of T cell antigen receptors (TCRs) with specific phenotypes (clonotypes), according to a study published online June 10 in Nature Immunology.

To examine how HLA-B*27 and HLA-B*57 can control HIV-1 infection in some individuals (controllers) but not others (progressors), Huabiao Chen, Ph.D., from the Massachusetts Institute of Technology in Boston, and colleagues examined the responses of restricted CD8+ T cells from treatment-naive controllers and progressors to HIV-1 and viral epitopes.

The researchers found that distinct TCR clonotypes were associated with better control of HIV-1 replication in vitro, enhanced cross-reactivity to epitope variants, and increased loading and delivery of perforin. This correlated with the distinct ability of controllers and progressors to inhibit viral replication via targeting of the immunodominant epitope of the group-associated antigen of HIV-1. In controllers and progressors, clonotype-specific differences were noted in antiviral efficacy for an immunodominant HLA-B*57-restricted response. The most effective clonotypes were dominantly selected in vivo in the controllers, while the least effective were dominantly selected in the progressors.

"Thus, the efficacy of such so-called 'protective alleles' is modulated by specific TCR clonotypes selected during natural infection, which provides a functional explanation for divergent HIV-1 outcomes," Chen and colleagues conclude.

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