JVI Accepts, published online ahead of print on 9 January 2008

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J. Virol. doi:10.1128/JVI.02260-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

MAGNITUDE, BREADTH AND FUNCTIONAL PROFILE OF T-CELL RESPONSES DURING HIV PRIMARY INFECTION WITH B AND BF VIRAL VARIANTS

Gabriela Turk, María Magdalena Gherardi, Natalia Laufer, Mónica Saracco, Renata Luzzi, Josephine H. Cox, Pedro Cahn, and Horacio Salomon^*

Centro Nacional de Referencia para el SIDA, Universidad de Buenos Aires, Buenos Aires, Argentina; Hospital Fernández, Buenos Aires, Argentina, Henry M Jackson Foundation/US Military HIV Research Program, Rockville, MD, USA

^* To whom correspondence should be addressed. Email: hsalomon{at}fmed.uba.ar.

The molecular pattern of the HIV epidemic in Argentina provides an appropriate scenario to study cellular immune responses in patients with non-clade B infection. We aimed to map T-cell responses in patients infected with BF recombinant variants and compare them with those of clade B patients. Sixteen recently infected patients were enrolled and grouped by viral subtype. Nef-specific responses were evaluated with a peptide matrix-based IFN- ELISPOT using B and BF overlapping peptides. Cross-clade and clade-specific responses were found. A correlation between B vs BF Nef-specific responses was identified. Detailed analysis at the single-peptide level revealed that BF patients show a narrower response but greater in magnitude. Nef immunodominant responses agreed with previous publications although the B loop was targeted in an unexpectedly high frequency. Putative HLA allele(s) restricting each positive response were determined. Single-peptide level screening with two different peptide sets uncovered discordant responses (mostly caused by peptide off-setting) and allowed detection of increased breadth. Positive responses identified by ELISPOT were further studied by ICS. These were almost exclusively mediated by CD8 T-cells. Characterization of concordant responses revealed that cells show distinct functional profiles, depending on the peptide presented. Lastly, quality (in terms of polyfunctionality) of T-cells was associated with better viral replication containment. Overall, inter-clade differences in the frequency of epitopes recognized, structural domains targeted and magnitude of responses were identified. Screening T-cell responses with multiple sets increased sensitivity. Further support to the notion of polyfunctional CD8+ T-cell requirement to better control viral replication is also provided.

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