311 T-cell Receptor Vbeta-repertoire of Immunodominant HIV-specific CD8+ T-cell Population D. Meyer-Olson*1, M. Altfeld1, K. W. Brady1, S. He1, P. Lee1, R. Dränert1, T. M. Allen1, M. M. Addo1, D. Strick1, E. S. Rosenberg1, B. D. Walker1, S. A. Kalams2 1Partners AIDS Res Ctr, Massachusetts Gen Hosp and Harvard Med Sch, Boston, MA and 2Vanderbilt Univ Med Ctr, Nashville, TN
Background: CD8+ T-cells recognizing HIV antigens are believed to be one important contributor of antiviral immune defense and are target to many vaccination strategies. Nevertheless, the knowledge about the T-cell receptor beta variable region (Vbeta) usage of antigen specific CD8+ T-cells in HIV infection is still limited.
Methods: To address this question, we analyzed the Vbeta-repertoire of dominant CD8+ T-cell responses by flow cytometry using antibodies identifying different Vbeta in combination with HLA class I tetramer staining ex vivo.
Results: Seven (7) patients (pts) with CD8 responses against the HLA-B8 restricted HIV nef epitope B8-FL8 (FLKEKGGL) showed broad usage of different Vbeta-families. Distinct Vbetas like Vbeta14 or Vbeta21.3 could be observed in the majority of pts, whereas others could not be observed at all. In some individuals, we detected expansions of single Vbetas up to 30% to 50% of the entire B8-FL8 specific repertoire. These data indicate substantial differences in the Vbeta-usage of HIV specific CD8+ T-cells. In one treated individual, we detected an expansion of a single Vbeta8+ population that comprised more than 50% of the B8-FL8 specific CD8+ T-cell repertoire. This Vbeta-population remained stable for at least 6 months. Sequencing of the T-cell receptor beta repertoire revealed that the B8-FL8 specific Vbeta8+ population was represented by a single clonotype. Analysis of 2 other untreated pts revealed major changes of the frequencies of B8-FL8 specific Vbetas during longitudinal observation.
Conclusions: Although still anecdotal, these observations may indicate adaptations of the epitope-specific CD8+ T-cell repertoire in response to the replicating virus and need further investigation. The analysis of the antigen specific Vbeta-repertoire ex vivo will enable us to better understand the kinetics of the adaptive CD8+ T-cell response, and its role in the course and pathogenesis of HIV infection.
