Many antigen‐specific T cell responses show profound V‐region biases in one or both chains of the TCR αβ heterodimer. We have examined how changes in residues within an MHC‐bound peptide can influence V‐region selection. Single‐chain TCR transgenic mice were derived using a β‐chain specific for the K b ‐restricted peptide from ovalbumin, OVA 257‐264 Transgenic T cells were stimulated in vitro using OVA 257‐264 or a single residue variant having a lysine to aspartic acid substitution at determinant position 7 (7D). Recent crystallographic analyses have shown that this variant residue is involved in direct contact with the TCR. Sequence analysis of the T cell populations showed that the majority OVA 257‐264 specific T cells used Vα10‐positive TCR while the majority of the 7D‐specific TCR expressed the Vα4 element. In both peptide responses we found that some cell lines appeared to be made up of more than one clone expressing the same Vα sequence but having limited variation at the V‐J junction. These results show that the TCR contact residues within the target peptide can influence V‐region bias and suggest that the first and second hypervariable regions of the TCR are directly or indirectly involved in determining peptide specificity.
|Number of pages||6|
|Journal||Immunology and Cell Biology|
|Publication status||Published - 1 Jan 1995|
- T cell receptor