Biased T cell receptor usage by L(d)-restricted, tum- peptide-specific cytotoxic T lymphocyte clones

J. C. Solheim, M. A. Alexander-Miller, J. M. Martinko, J. M. Connolly

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Abstract

We have investigated the TCR gene usage in a panel of H-2L(d)-restricted, tum- peptide-specific CTL clones. These clones possess identical MHC restriction and peptide specificity, yet they vary dramatically in the amount of peptide required to sensitize targets for recognition. We previously demonstrated a precise quantitative correlation between the determinant density requirement of a given clone and the CD8 dependency. In this study we sequenced polymerase chain reaction copies of the TCR mRNA used by these clones, not only to correlate TCR structure with recognition of a specific class I/peptide complex, but also to determine if the functional affinity differences between these clones is reflected in the TCR gene products used. The number of TCR Vβ, Vα, and Jα region gene segments expressed by these clones is very limited. Twelve of 17 clones express Vβ8 at comparable levels on the cell surface. Using PCR amplification of cDNA templates, cloning, and dideoxy sequencing, we have obtained the nucleotide sequence of the TCR V- (D)-J regions in seven of the Vβ8+ clones. Two of the clones use Vβ8.2 and identical Jα gene segments. Three of the five Vβ8.3+ clones express identical Vα and Jα gene products and the other two use similar Vα chains and Jα chains with a shared motif in the predicted CDR3 region. Although no clear correlation between TCR gene usage and CD8 dependency was seen, the range of TCR gene usage in the tum- peptide-specific, L(d)-restricted immune response is strikingly narrow and suggests a coselection of the α- and β- chains for recognition of the class I/peptide complex.

Original languageEnglish (US)
Pages (from-to)800-811
Number of pages12
JournalJournal of Immunology
Volume150
Issue number3
StatePublished - Jan 1 1993

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Solheim, J. C., Alexander-Miller, M. A., Martinko, J. M., & Connolly, J. M. (1993). Biased T cell receptor usage by L(d)-restricted, tum- peptide-specific cytotoxic T lymphocyte clones. Journal of Immunology, 150(3), 800-811.