Competitive inhibition in vivo and skewing of the T cell repertoire of antigen-specific CTL priming by an anti-peptide-MHC monoclonal antibody.
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 Vbeta usage of Ag-specific CTL. Ab blocking skews the proportion of high avidity cells emerging from immunization. Surprisingly, Vbeta7-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.
Chung
D H
DH
Laboratory of Immunology, National Institute of Allergy and Infectious Disease, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Belyakov
I M
IM
Derby
M A
MA
Wang
J
J
Boyd
L F
LF
Berzofsky
J A
JA
Margulies
D H
DH
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D015488:HIV Antigens / Q000276:immunology / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000276:immunology* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013234:Stem Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D064532:Histocompatibility Antigen H-2D; C416863:KP15 monoclonal antibody; D009842:Oligopeptides; D016693:Receptors, Antigen, T-Cell, alpha-beta