Immunodominance, competition and evolution in immunological responses to helminth parasite antigens

Abstract

SUMMARYThe paper describes the development and analysis of a mathematical framework for the study of the within-host population dynamics of the interaction between macroparasites and the human immune system. Simple models of this interaction based on the proliferation of T cell clones specific to parasite antigen, and the impact of clonal expansion on parasite survival, capture the basic features of age-related changes in worm loads within human communities. The model is generalized to multiple epitopes on a single antigen, and reveals competitive exclusion amongst T cells, with a single clone becoming immunodominant in the absence of cross-reactive responses and genetic variation. The introduction of genetic heterogeneity and concomitant variability in the immunogenicity of specific epitopes induces additional complexity into the dynamical interaction. Most importantly, multiple epitope models with antigenic variation suggest that the immunodominant response may not necessarily be targeted at the epitope at which some strains show the greatest immunogenicity. High immunogenicity at a particular epitope can be masked by genetic variability even though many of the variants are more immunogenic at this epitope by comparison with the epitope to which the immunodominant immunological response is directed.