T Cell Receptor (Tcr)-Mediated Repertoire Selection and Loss of Tcr Vβ Diversity during the Initiation of a Cd4+ T Cell Response in Vivo

• Main Authors: Fassò, Marcella, Anandasabapathy, Niroshana, Crawford, Frances, Kappler, John, Fathman, C. Garrison, Ridgway, William M.
• Format: Text
• Language: English
• Published: The Rockefeller University Press 2000
• Subjects: Original Article; Sperm whale
• Online Access: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213496; http://www.ncbi.nlm.nih.gov/pubmed/11120769

We recently described a novel way to isolate populations of antigen-reactive CD4+ T cells with a wide range of reactivity to a specific antigen, using immunization with a fixed dose of nominal antigen and FACS® sorting by CD4high expression. Phenotypic, FACS®, functional, antibody inhibition, and major histocompatibility complex–peptide tetramer analyses, as well as T cell receptor Vβ sequence analyses, of the antigen-specific CD4high T cell populations demonstrated that a diverse sperm whale myoglobin 110–121–reactive CD4+ T cell repertoire was activated at the beginning (day 3 after immunization) of the immune response. Within 6 d of immunization, lower affinity clones were lost from the responding population, leaving an expanded population of oligoclonal, intermediate affinity (and residual high affinity) T cells. This T cell subset persisted for at least 4 wk after immunization and dominated the secondary immune response. These data provide evidence that CD4+ T cell repertoire selection occurs early in the immune response in vivo and suggest that persistence and expansion of a population of oligoclonal, intermediate affinity T cells is involved in CD4+ T cell memory.