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Volume 9 Supplement 2

AIDS Vaccine 2012

Understanding the precursor frequencies of HIV-1 specific CD4+ T cells in seronegative donors

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HIV-1 specific T cell responses are detectable amongst a proportion of HIV-1 exposed, seronegative individuals. Previous studies from our group have demonstrated these responses are predominately mediated by CD4+ T cells and can be mapped and titrated at the peptide level. Curiously, approximately 1 in 4 HIV-1 un-exposed seronegative donors also have demonstrable HIV-1 specific T cell responses. This observation raises a number of questions regarding the ontogeny of pre-existing HIV-1 specific T cells and their potential role in the acquisition of HIV-1.


A highly sensitive T cell library method was used to screen the naïve, central and effector memory CD4+ T cell subsets from 10 healthy, HIV-1 seronegative, leukapharesis donors. 192 cell lines per subset were screened against pools of overlapping 18mer peptides, spanning the entire HIV-1 proteome and proliferative responses quantified using tritiated thymidine incorporation.


HIV-1 specific CD4+ T cell response were detectable within the CD4+ T cell memory compartments of all 10 subjects tested, albeit at low frequency. HIV-1 specific CD4+ T cell responses spanned the entire HIV-1 proteome and were typically of low avidity. There was considerable variability between donors both in the proteins recognized and precursor frequencies of HIV-1 specific T cell responses. However, across all subsets tested CD4+ T cells specific for HIV-1 envelope appeared to exist at the highest precursor frequency, with Pol seemingly the least frequently targeted.


We show HIV-1 specific CD4+ T cells to be detectable within the memory compartment of all 10 donors tested. In the absence of known prior exposure to HIV-1 these observations are indicative of low level cross reactivity within the immune system. The use of the T cell library technique to interrogate the naïve and memory precursor frequencies of HIV-1 specific T cells should prove beneficial in the design of novel therapeutic vaccines.

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Correspondence to SL Campion.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Cell Response
  • Tritiated Thymidine
  • 18mer Peptide
  • Level Cross
  • Cell Library