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

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 n...

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Bibliographic Details
Published in:PloS one 2013-12, Vol.8 (12), p.e80045-e80045
Main Authors: Roider, Julia, Kalteis, Anna-Lena, Vollbrecht, Thomas, Gloning, Lisa, Stirner, Renate, Henrich, Nadja, Bogner, Johannes R, Draenert, Rika
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
Adaptation
Adaptations
Adult
AIDS
Alleles
Amino acid sequence
Antiretroviral agents
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
Cohort Studies
Development and progression
Epitopes
Female
Gag protein
Gene Products, gag - genetics
Gene Products, gag - immunology
Genetic aspects
Histocompatibility antigen HLA
Histocompatibility antigens
HIV
HIV infection
HIV Infections - genetics
HIV Infections - immunology
HIV-1 - genetics
HIV-1 - immunology
HLA histocompatibility antigens
HLA-B Antigens - genetics
HLA-B Antigens - immunology
Human immunodeficiency virus
Humans
Immunity, Cellular - genetics
Immunodominance
Lymphocytes
Lymphocytes T
Male
Middle Aged
Mutation
nef Gene Products, Human Immunodeficiency Virus - genetics
nef Gene Products, Human Immunodeficiency Virus - immunology
Nef protein
Physiological aspects
Population genetics
T cell receptors
T cells
Titration
Vaccines
Viruses
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0080045