Selection for amino acid sequence and J beta element usage in the beta chain of DBA/2V beta b- and DBA/2V beta a-derived myoglobin-specific T cell clones.
Previous experiments in our laboratory have demonstrated that there is a marked restriction on the TCR beta-chain usage in DBA/2 mice in response to the sperm whale myoglobin (SpWMb) determinant 110-121, predominated by the use of the V beta 8.2 gene element. We analyzed the response of mice that had been genetically depleted of V beta 8+ T cells by generating a DBA/2 line that carries the V beta a TCR haplotype. Despite the very limited TCR repertoire expressed by DBA/2V beta a mice, they made an excellent response after immunization with the SpWMb 110-121 peptide. Data presented in this manuscript demonstrate that there is an equally restricted TCR V beta-chain utilization in the T-cell response to the determinant SpWMb 110-121 in DBA/2V beta a mice. Unexpectedly, there was a shift of MHC restriction of this determinant to T cells in the V beta a strain when compared with the V beta b strain of DBA/2 mice. We had previously demonstrated that DBA/2 mice utilized both the hybrid E alpha dA beta d MHC molecule as well as the conventional A alpha dA beta d molecule as presenting elements in response to SpWMb 110-121. Data presented in this manuscript demonstrate that the T-cell response in DBA/2V beta a mice is entirely restricted by the A alpha dA beta d MHC class II molecule. By analyzing a panel of SpWMb 110-121-specific T-cell clones from DBA/2V beta a mice, we were able to study the TCR repertoire expressed on T cells from mice that lack the V beta 8.2 gene. The V beta usage by the panel of clones analyzed was remarkably homogeneous. Thirteen of the 17 clones analyzed used the V beta 1 gene segment. Perhaps more striking was the junctional region nucleotide and amino acid sequences that were shared among these clones and that were similar to the V beta 8.2 clones analyzed previously. All clones assayed used the J beta 2.6 element, as did the great majority of the V beta 8.2 clones analyzed from DBA/2 (and B10.D2) V beta b mice. Importantly, in each strain of mice, irrespective of the V beta utilized, each TCR appeared to have selected an acidic amino acid in the beta-chain at position 100.(ABSTRACT TRUNCATED AT 400 WORDS)
Ruberti
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Department of Medicine, Stanford University Medical School, CA 94305.
Paragas
V
V
Kim
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D
Fathman
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CG
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D002999:Clone Cells; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009211:Myoglobin / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D009211:Myoglobin; D016693:Receptors, Antigen, T-Cell, alpha-beta