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Cutting Edge: The Relative Distribution of T Cells Responding to Chemically Dominant or Minor Epitopes of Lysozyme Is Not Affected by CD40-CD40 Ligand and B7-CD28-CTLA-4 Costimulatory Pathways¹

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

We examined the frequencies and specificities of the CD4⁺ T cell responses to the protein hen egg white lysozyme in mice deficient in the CD40-CD40 ligand or B7-CD28 costimulatory pathways. The frequency of T cells was decreased by between 3- and 4-fold in CD40^-/- mice, and 12-fold in B7-1/B7-2^-/- mice, but surprisingly, the relative distribution of T cells responding to peptides that were presented at levels that differed by >250-fold was similar. We also examined the CD4 response after blocking the regulatory molecule CTLA-4 during immunization. We observed no difference in either the frequency or specificity of the CD4⁺ T cell response if CTLA-4 was blocking during priming. Thus, the T cell response was generated toward the constellation of chemically dominant and subdominant epitopes as a whole, and did not discriminate among them based on their relative abundance.

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