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Title: The challenges of modelling antibody repertoire dynamics in HIV infection

Antibody affinity maturation by somatic hypermutation of B-cell immunoglobulin variable region genes has been studied for decades in various model systems using well-defined antigens. While much is known about the molecular details of the process, our understanding of the selective forces that generate affinity maturation are less well developed, particularly in the case of a co-evolving pathogen such as HIV. Despite this gap in understanding, high-throughput antibody sequence data are increasingly being collected to investigate the evolutionary trajectories of antibody lineages in HIV-infected individuals. Here, we review what is known in controlled experimental systems about the mechanisms underlying antibody selection and compare this to the observed temporal patterns of antibody evolution in HIV infection. In addition, we describe how our current understanding of antibody selection mechanisms leaves questions about antibody dynamics in HIV infection unanswered. Without a mechanistic understanding of antibody selection in the context of a co-evolving viral population, modelling and analysis of antibody sequences in HIV-infected individuals will be limited in their interpretation and predictive ability.
 [1] ;  [2]
  1. Univ. of California, Berkeley, CA (United States)
  2. Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Publication Date:
OSTI Identifier:
Report Number(s):
Journal ID: ISSN 0962-8436
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Philosophical Transactions of the Royal Society of London, Series B: Biological Sciences
Additional Journal Information:
Journal Volume: 370; Journal Issue: 1676; Journal ID: ISSN 0962-8436
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org:
Country of Publication:
United States
59 BASIC BIOLOGICAL SCIENCES HIV; evolution; immunology