T cell receptor V alpha bias can be determined by TCR-contact residues within an MHC-bound peptide.
Many antigen-specific T cell responses show profound V-region biases in one or both chains of the TCR alpha beta 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 beta-chain specific for the Kb-restricted peptide from ovalbumin, OVA257-264. Transgenic T cells were stimulated in vitro using OVA257-264 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 OVA257-264-specific T cells used V alpha 10-positive TCR while the majority of the 7D-specific TCR expressed the V alpha 4 element. In both peptide responses we found that some cell lines appeared to be made up of more than one clone expressing the same V alpha 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.
Sterry
S J
SJ
Department of Pathology and Immunology, Monash Medical School, Prahran, Victoria, Australia.
Kelly
J M
JM
Turner
S J
SJ
Carbone
F R
FR
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D008285:Major Histocompatibility Complex / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin