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Original Article |
Correspondence to: C. Garrison Fathman, Department of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, CCSR Building, Rm. 2225, 300 Pasteur Dr., Stanford, CA 94305-5166. Tel:650-723-7887 Fax:650-725-1958 E-mail:cfathman{at}leland.stanford.edu.
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 Vß 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.
Key Words: T cells, clonal selection, T cell receptor, major histocompatibility complex class II tetramers, immune response
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