Effective T helper cell responses against retroviruses: are all clonotypes equal?

The critical importance of CD4(+) T cells in coordinating innate and adaptive immune responses is evidenced by the susceptibility to various pathogenic and opportunistic infections that arises from primary or acquired CD4(+) T cell immunodeficiency, such as following HIV-1 infection. However, despite the clearly defined roles of cytotoxic CD8(+) T cells and antibodies in host protection from retroviruses, the ability of CD4(+) T cells to exert a similar function remains unclear. Recent studies in various settings have drawn attention to the complexity of the T cell response within and between individuals. Distinct TCR clonotypes within an individual differ substantially in their response to the same epitope. Functionally similar, "public" TCR clonotypes can also dominate the response of different individuals. TCR affinity for antigen directly influences expansion and differentiation of responding T cells, also likely affecting their ultimate protective capacity. With this increasing understanding of the parameters that determine the magnitude and effector type of the T cell response, we are now better equipped to address the protective capacity against retroviruses of CD4(+) T cell clonotypes induced by natural infection or vaccination.