Human Immunodeficiency Virus-Specific Gamma Interferon Enzyme-Linked Immunospot Assay Responses Targeting Specific Regions of the Proteome during Primary Subtype C Infection Are Poor Predictors of the Course of Viremia and Set Point

Abstract

It is unknown whether patterns of human immunodeficiency virus (HIV)-specific T-cell responses during

Fluidity of HIV-1-Specific T-Cell Responses during Acute and Early Subtype C HIV-1 Infection and Associations with Early Disease Progression

“…2B). We have previously reported on specific Nef epitopes recognized at 12 weeks postinfection (22), and when responses were normalized, taking into account the amino acid length of the protein for each responder, Nef was the most immunogenic protein at all time points, corroborating findings of Streeck et al (48) and Masemola et al (34). The highest density of targeted peptides was embedded within the conserved central region of Nef between amino acids 52 to 171 (22).…”

“…Viral load was measured with the COBAS Amplicor HIV-1 monitor test, version 1.5 (Roche Diagnostics, Branchburg, NJ), and the CD4 ϩ count was measured by flow cytometry. The studied subjects were estimated to have been infected for a median duration of 6 weeks, ranging from 2 to 15 weeks postinfection at enrollment (22). The median plasma viral load at enrollment was 75,600 HIV RNA copies/ml (range, 547 to 5,510,000), and the median CD4 ϩ count was 494 cells/mm 3 (range, 197 to 989).…”

“…HIV-1-specific T-cell responses were quantified by IFN-␥ ELISPOT assay using a set of 432 overlapping peptides spanning the entire HIV-1 C proteome arranged in a pool matrix format as previously described (22,34). Briefly, freshly isolated PBMC were stimulated with HIV-1 peptide pools (2 g/ml), cytomegalovirus, Epstein-Barr virus, and influenza virus (CEF) pools (1 g/ml), and phytohemagglutinin (4 g/ml), incubated overnight at 37°C with 5% CO 2 , and developed as previously described.…”

“…However, the temporal nature of epitope-specific responses that associate with viral control has not been explored. Recently, we found no association between the magnitude and breadth of gamma interferon (IFN-␥) enzymelinked immunospot (ELISPOT) assay responses at a static 3-month time point with the viral set point at 12 months (22). The unpredictability of early T-cell responses with later viral control could be a result of HIV variability resulting in epitope escape from humoral and T-cell pressure (1,8).…”

Antibodies and Lentiviruses That Specifically Recognize a T Cell Epitope Derived from HIV-1 Nef Protein and Presented by HLA-C

“…In addition, HIV-1 Nef was reported to be the single most immunogenic protein of HIV-1, inducing CTL responses in 91.3% of individuals across four different human ethnicities (17). In a different study, Nefassociated responses were found to be the most dominant at 12 wk postinfection (18). These findings further suggest that in most individuals, Nef-derived peptides are properly processed and presented on the surfaces of infected cells.…”