Identifying the earliest virus-specific T cell responses during acute HIV-1 infection and the regions of HIV-1 targeted by these responses represents a critical component in the understanding of HIV-1 pathogenesis and the guidance of HIV-1 vaccine design. The Immunology Core will perform standard assays of HIVspecific adaptive immunity on all subjects with primary HIV-1 infection enrolled in this program and will enter these data into the overall database. Furthermore, the Core will provide access to multiparameter flow cytometers and biohazard cell sorting facilities to perform the experiments described in the individual projects. The Immunology Core will implement strict quality control mechanisms to ensure that these assays are performed following defined Standard Operating Procedures (SOP). The data from the characterization of the breadth, magnitude and specificity of the HIV-1-specific T cell response in acute HIV-1 infection generated by the Immunology Core will provide the baseline immunology data to select individual study subjects for the proposed specific studies of viral sequence evolution (Project 3), antigen processing and T cell function (Project 2). Furthermore, the parallel studies of adaptive and innate immunity (Project 1) will allow for the analysis of T cell function in the context of innate immune function. The proposed assays will incorporate a newly designed set of overlapping HIV-1 peptides spanning the entire expressed clade B consensus sequence, as well as all minor variants present in at least 5 -10% of the published HIV-1 clade B sequences in the Los Alamos National Database (""""""""toggled"""""""" peptides). This will allow us to comprehensively characterize HIV-1-specific T cell responses during acute HIV-1 infection, as well as their evolution over time. HIV-1-specific T cell responses will be characterized using an approach combining the IFN-yElispot assay and the Bio-Plex Cytokine Assay at baseline, as well as 2, 6 and 12 months following acute infection. This Core will be closely linked to the Administrative Core though the database and clinical specimen repository, and will be a key component serving the Pis of each of the proposed scientific research programs. The following aims will be addressed by the Immunology Core: 1. Characterization of HIV-1-specific T cell responses directed against the entire expressed HIV-1 clade B sequence on the single peptide level 2. Characterization CD8+ T cell responses directed against optimal HIV-1-specific CD8+ T cell epitopes described for the subjects'HLA class I haplotype 3. Inclusion of these data into a relational database that will allow for identification individual study subjects for the specific research projects proposed.
Showing the most recent 10 out of 47 publications
