Evaluating the role of early HIV-specific T and B cell interactions in predetermining downstream antibody function.

Evaluating the role of early HIV-specific T and B cell interactions in predetermining downstream antibody function.

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A small proportion of HIV-1 infected persons develop broadly neutralising antibodies (bNABs) after years of infection. In contrast, antibodies able to mediate effector functions through innate immune cells are more commonly found in HIV infected people. Antibodies are generated by B cells; upon antigen stimulation, B cells differentiate into antibody secreting cells and memory B cells. Previous studies have indicated that HIV leads to a perturbation of the B cell compartment but to what extent these perturbations contribute to the delayed functional antibody responses is still not clear.

Previous literature shows that bNABs undergo many rounds of affinity maturation a process that takes place in the germinal centre and may require help from T follicular helper cells (TfH). It is therefore conceivable that TfH cells may be crucial in the generation of HIV- specific antibodies.

Recently, a number of studies have addressed the relationship between Tfh cell frequencies, phenotypes and quality, with T cell help and antibody breadth. However, the majority of these studies looked at the total Tfh population without demonstrating the contribution of HIV-specific subsets and function to down-stream antibody responses.

Oyaro’s project hypothesises that HIV-specific CXCR5+CD4+ T cells that arise during acute HIV infection and persist will predict the quality of downstream antibody function in chronic HIV-1 infection. Generally, we seek to evaluate the role of early HIV-specific TfH and B cell phenotypes in predetermining the subsequent development of antibodies both with neutralising and non-neutralising function. More specifically, we pursue to utilise flow cytometry and serological based assays to determine HIV-specific TfH cells and HIV-specific B-cell subsets and functions in early HIV infection and how these correlate to downstream antibody function. The outcome of this project will improve our understanding on the role of early HIV-specific T and B cells in generating antibodies with “protective” function and this may accelerate the development of antibody-based HIV vaccines.