J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/07/83/07 $2.00
Volume 186, Number 1, July 7, 1997 83-89

Epitope-dependent Selection of Highly Restricted or Diverse T Cell Receptor Repertoires in Response to Persistent Infection by Epstein-Barr Virus

By Pedro-Otavio de Campos-Lima,^* Victor Levitsky,^* Martha P. Imreh,^* Riccardo Gavioli, and Maria G. Masucci^*

From the ^* Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77, Stockholm, Sweden; and  Institute of Biochemistry and Molecular Biology, University of Ferrara Medical School, 44100 Ferrara, Italy

The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11-restricted epitopes in the Epstein-Barr virus (EBV) nuclear antigen-4 were investigated in four healthy virus carriers. The response to the subdominant epitope (EBNA4 399-408, designated AVF) was highly restricted with conserved V usage and identical length and amino acid motifs in the third complementarity-determining regions (CDR3), while a broad repertoire using different combinations of TCR-/ V and J segments and CDR3 regions was selected by the immunodominant epitope (EBNA4 416-424, designated IVT). Distinct patterns of interaction with the A11-peptide complex were revealed for each AVF- or IVT-specific TCR clonotype by alanine scanning mutagenesis analysis. Blocking of cytotoxic function by antibodies specific for the CD8 coreceptor indicated that, while AVF-specific TCRs are of high affinity, the oligoclonal response to the IVT epitope includes both low- and high-affinity TCRs. Thus, comparison of the memory response to two epitopes derived from the same viral antigen and presented through the same MHC class I allele suggests that immunodominance may correlate with the capacity to maintain a broad TCR repertoire.

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