Thomas W McCloskey1, Viraga Haridas, Rajendra Pahwa, Savita Pahwa. 1. North Shore Long Island Jewish Research Institute/New York University School of Medicine, Immunology and Inflammation Center of Excellence, Manhasset, New York 11030, USA.
Abstract
OBJECTIVE: Analysis of the T cell receptor V beta repertoire during HIV infection reveals expansions in multiple V beta families of CD8 T cells, but their antigenic specificity is ill-defined. We sought to determine the TCR V beta repertoire of HIV specific CD8 T lymphocytes in infected children. DESIGN/ METHODS: We performed flow cytometry to examine TCR V beta families as identified by specific monoclonal antibodies and binding of HIV peptide loaded tetrameric MHC complexes in peripheral blood samples from a group of HIV infected children. RESULTS: Simultaneous assessment of 12 selected expanded V beta families amongst nine HIV infected patients for tetramer binding revealed only one child in whom the expanded V beta population bound HIV Gag or Pol tetramers. In four HIV infected children, percentage tetramer binding cells was determined in 21 TCR V beta families. The tetramer binding cells of three children exhibited a widely distributed TCR V beta repertoire while in the fourth patient they were preferentially localized within two TCR V beta families. Repeat analysis revealed that the TCR V beta repertoire of tetramer binding cells was stable. CONCLUSIONS: These data provide evidence that the HIV-specific CD8 T cell response in children is usually distributed widely among many different TCR V beta families. The heterogeneity of the TCR V beta repertoire usage by the antigen specific CD8 T cells may reflect the dynamic interaction between host and pathogen during the course of HIV infection and may be influenced by the rate of viral mutation, CD4 T cell helper activity, or other factors.
OBJECTIVE: Analysis of the T cell receptor V beta repertoire during HIV infection reveals expansions in multiple V beta families of CD8 T cells, but their antigenic specificity is ill-defined. We sought to determine the TCR V beta repertoire of HIV specific CD8 T lymphocytes in infected children. DESIGN/ METHODS: We performed flow cytometry to examine TCR V beta families as identified by specific monoclonal antibodies and binding of HIV peptide loaded tetrameric MHC complexes in peripheral blood samples from a group of HIV infectedchildren. RESULTS: Simultaneous assessment of 12 selected expanded V beta families amongst nine HIV infectedpatients for tetramer binding revealed only one child in whom the expanded V beta population bound HIV Gag or Pol tetramers. In four HIV infectedchildren, percentage tetramer binding cells was determined in 21 TCR V beta families. The tetramer binding cells of three children exhibited a widely distributed TCR V beta repertoire while in the fourth patient they were preferentially localized within two TCR V beta families. Repeat analysis revealed that the TCR V beta repertoire of tetramer binding cells was stable. CONCLUSIONS: These data provide evidence that the HIV-specific CD8 T cell response in children is usually distributed widely among many different TCR V beta families. The heterogeneity of the TCR V beta repertoire usage by the antigen specific CD8 T cells may reflect the dynamic interaction between host and pathogen during the course of HIV infection and may be influenced by the rate of viral mutation, CD4 T cell helper activity, or other factors.
Authors: Dirk Meyer-Olson; Kristen W Brady; Melissa T Bartman; Kristin M O'Sullivan; Brenna C Simons; Joseph A Conrad; Coley B Duncan; Shelly Lorey; Atif Siddique; Rika Draenert; Marylyn Addo; Marcus Altfeld; Eric Rosenberg; Todd M Allen; Bruce D Walker; Spyros A Kalams Journal: Blood Date: 2005-12-01 Impact factor: 22.113