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Competitive Inhibition In Vivo and Skewing of the T Cell Repertoire of Antigen-Specific CTL Priming by an Anti-Peptide-MHC Monoclonal Antibody

Doo Hyun Chung^1,*, Igor M. Belyakov, Michael A. Derby, Jian Wang^*, Lisa F. Boyd^*, Jay A. Berzofsky and David H. Margulies^2,*

^* Laboratory of Immunology, National Institute of Allergy and Infectious Disease, and Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892

We have recently described a mAb, KP15, directed against the MHC-I/peptide molecular complex consisting of H-2D^d and a decamer peptide corresponding to residues 311–320 of the HIV IIIB envelope glycoprotein gp160. When administered at the time of primary immunization with a vaccinia virus vector encoding gp160, the mAb blocks the subsequent appearance of CD8⁺ CTL with specificity for the immunodominant Ag, P18-I10, presented by H-2D^d. This inhibition is specific for this particular peptide Ag; another H-2D^d-restricted gp160 encoded epitope from a different HIV strain is not affected, and an H-2L^d-restricted epitope encoded by the viral vector is also not affected. Using functional assays and specific immunofluorescent staining with multivalent, labeled H-2D^d/P18-I10 complexes (tetramers), we have enumerated the effects of blocking of priming on the subsequent appearance, avidity, and TCR V usage of Ag-specific CTL. Ab blocking skews the proportion of high avidity cells emerging from immunization. Surprisingly, V7-bearing Ag-specific TCR are predominantly inhibited, while TCR of several other families studied are not affected. The ability of a specific MHC/peptide mAb to inhibit and divert the CD8⁺ T cell response holds implications for vaccine design and approaches to modulate the immune response in autoimmunity.

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