The T cell receptor repertoire influences V beta element usage in response to myoglobin.
T cell clones recognizing the sperm whale myoglobin (SpWMb) epitope 110-121 in association with H-2d major histocompatibility complex class II molecules display a very limited heterogeneity of T cell receptor (TCR) V beta usage in DBA/2 mice. All clones previously tested used the same V beta 8.2 gene segment and very restricted junctional regions. To investigate the significance of this observation in vivo, we immunized DBA/2 mice with the intact SpW Mb protein or peptide 110-121. Only the V beta 8+ T cells showed any significant response to the 110-121 epitope. The response to peptide 110-121 was then analyzed in mice which, either as a consequence of antibody depletion or through genetic deletion of TCR V beta genes, lacked V beta 8+ peripheral T cells. DBA/2 mice depleted of V beta 8+ T cells by antibody treatment responded poorly to the 110-121 peptide, and only at high antigen concentrations. In contrast, DBA/2V beta a mice (homozygous for a deletion of multiple V beta gene segments including the V beta 8 family) made a response at least as great as that made by DBA/2 mice, even though the DBA/2V beta a mice had a very restricted TCR V beta repertoire compared with DBA/2 mice. Mechanisms which might determine differences in the 110-121 specific response of DBA/2, DBA/2V beta a and F23.1-treated DBA/2 mice are discussed.
Ruberti
G
G
Department of Medicine, Stanford University School of Medicine, California 94305.
Gaur
A
A
Fathman
C G
CG
Livingstone
A M
AM
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002478:Cells, Cultured; D002872:Chromosome Deletion; D003433:Crosses, Genetic; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006720:Homozygote; D007700:Kinetics; D007739:L Cells / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D046911:Macromolecular Substances; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009211:Myoglobin / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D000949:Histocompatibility Antigens Class II; D046911:Macromolecular Substances; D009211:Myoglobin; D011948:Receptors, Antigen, T-Cell