T-cell receptor capable of recognising an antigen from cytomegalovirus
The present invention provides a T-cell receptor (TCR) which binds to a peptide from the cytomegalovirus (CMV) phosphoprotein pp65 having the amino acid sequence NLVPMVATV (SEQ ID No. 1) when presented by a major histocompatability complex (MHC) molecule. The present invention also provides a nucleotide sequence encoding such a TCR, a vector comprising such a nucleotide sequence and its use to produce a CMV-specific T-cell. The present invention also provides the use of CMV-specific T-cell for cellular immunotherapy.
1. An isolated T-cell receptor (TCR) which binds to a peptide from the cytomegalovirus (CMV) phosphoprotein pp65 having the amino acid sequence NLVPMVATV (SEQ ID NO: 1) when presented by a major histocompatibility complex (MHC) molecule, the TCR comprising an α chain and a β chain,
wherein the α chain comprises three complementarity determining regions (CDRs) having the following amino acid sequences:
(SEQ ID NO: 4)
CDR1α - SSNFYA,
(SEQ ID NO: 5)
CDR2α - MTLNGD,
and
(SEQ ID NO: 2)
CDR3α - ARNTGNQFYFGTGTSLTVIPN,
and
wherein the β chain comprises three complementarity determining regions (CDRs) having the following amino acid sequences:
(SEQ ID NO: 6)
CDR1β - MNHEY,
(SEQ ID NO: 7)
CDR2β - SVGAGI,
and
(SEQ ID NO: 3)
CDR3β - ASSFQTGASYGYTFGSGTRLTVL.
2. The TCR according to claim 1 which comprises the amino acid sequence shown as SEQ ID NO: 8 or a variant thereof having at least 80% amino acid sequence identity.
3. The TCR according to claim 1 which comprises one or more mutations at the TCR α chain/β chain interface, such that when the TCR α chain and β chain are expressed in a T-cell, the frequency of mis-pairing between these chains and the endogenous TCR α chain and β chain is reduced.
4. The TCR according to claim 3 , wherein the constant region domains of the α chain and β chain each comprise an additional cysteine residue, enabling the formation of an extra disulphide bond between the αchain and the β chain.