title: Adaptation of CD8 T cell responses to changing HIV-1 sequences in a cohort of HIV-1 infected individuals not selected for a certain HLA allele.
abstract: HIV evades CD8 T cell mediated pressure by viral escape mutations in targeted CD8 T cell epitopes. A viral escape mutation can lead to a decline of the respective CD8 T cell response. Our question was what happened after the decline of a CD8 T cell response and - in the case of viral escape - if a new CD8 T cell response towards the mutated antigen could be generated in a population not selected for certain HLA alleles. We studied 19 antiretroviral-naïve HIV-1 infected individuals with different disease courses longitudinally. A median number of 12 (range 2-24) CD8 T cell responses towards Gag and Nef were detected per study subject. A total of 30 declining CD8 T cell responses were studied in detail and viral sequence analyses showed amino acid changes in 25 (83%) of these. Peptide titration assays and definition of optimal CD8 T cell epitopes revealed 12 viral escape mutations with one de-novo response (8%). The de-novo response, however, showed less effector functions than the original CD8 T cell response. In addition we identified 4 shifts in immunodominance. For one further shift in immunodominance, the mutations occurred outside the optimal epitope and might represent processing changes. Interestingly, four adaptations to the virus (the de-novo response and 3 shifts in immunodominance) occurred in the group of chronically infected progressors. None of the subjects with adaptation to the changing virus carried the HLA alleles B57, B*58:01 or B27. Our results show that CD8 T cell responses adapt to the mutations of HIV. However it was limited to only 20% (5 out of 25) of the epitopes with viral sequence changes in a cohort not expressing protective HLA alleles.
authors: Department of Infectious Diseases, Medizinische Klinik und Poliklinik IV der Ludwig-Maximilians-University, Munich, Germany.
authors: Julia
authors: J
authors: Roider
authors: Anna-Lena
authors: AL
authors: Kalteis
authors: Thomas
authors: T
authors: Vollbrecht
authors: Lisa
authors: L
authors: Gloning
authors: Renate
authors: R
authors: Stirner
authors: Nadja
authors: N
authors: Henrich
authors: Johannes R
authors: JR
authors: Bogner
authors: Rika
authors: R
authors: Draenert
mesh_terms: D000328:Adult; D000483:Alleles; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
chemical_list: D015683:Gene Products, gag; D015235:HLA-B Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1