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50 Nef-Specific T-Cell Responses in HIV-Infected African-American (A-A) and Hispanic (H) Adolescents
A. Bansal, D. Ritter, S. Sabbaj, C. Perkins, B. Edwards, B. Korber, R. Kaslow, C. Wilson, P. Goepfert, and M. Mulligan*
Univ. of Alabama at Birmingham, USA
Background: Most prior reports of CTL epitopes focused on Caucasian (Cauc) adults. Characterization of CTL responses to HIV proteins in other racial/ethnic groups is highly relevant for vaccine research. Nef is a moderately conserved 206-aa protein expressed in HIV-infected cells. We evaluated Nef-specific T-cell responses in predominantly A-A and H adolescents.
Methods: Adolescents were recruited from the REACH study of the NICHD Adolescent Medicine HIV/AIDS Research Network. PBMC were stimulated with 2 pools of 10 peptides (20-mers overlapping by 10) spanning 100-aa fractions of HIV-1/Bru Nef or the individual peptides. An ELISPOT assay was used to quantify interferon-gamma spot-forming cells (SFC). A positive response was defined as >100 net SFC/million PBMC (the mean ( SD of unstimulated PBMC).
Results: Ninety adolescents with chronic HIV infection were enrolled: 53% female, 70% A-A, 18% H, and 12% Cauc or other. Median values were: age, 19; VL, 3,250; CD4, 528. PBMC from 32/88 (36%) and 37/88 (42%) of the subjects who could be evaluated gave positive responses to the N- and C-terminal Nef peptide pools, respectively. Twenty-four percent of subjects responded to both pools, 31% to a single pool, and 45% to neither pool. In positive subjects, the mean net SFC/million PBMC for the N- and C-terminal pools was 383 and 393, respectively. For 17/88 (19%), the magnitude of the Nef response was greater than that of pools spanning Gag, Pol, and Env. In 6 of those 26 (23%), response magnitude was >1,000 SFC/million PBMC. In 60 representative subjects, 50% had positive responses distributed over 15 (75%) of the 20 individual Nef 20-mers. Dominant peptides were aa 131(150-GVRYPLTFGWCYKLVPVEPD (14/60, 23%) and aa 71(90-PQVPLRPMTYKAAVDLSHFL (12/60, 20%). These peptides were previously shown in Cauc to be restricted by multiple MHC alleles.
Conclusions: We identified Nef-specific T-cell responses of considerable magnitude and breadth in a cohort of predominantly A-A and H HIV+ adolescents. The fine specificity and MHC restriction of the Nef epitopes are being determined.
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