Human immunodeficiency virus-specific T cell receptors
Engineered TCR molecules specific to retroviral peptide/HLA complexes guide direct killing and/or enable robust immune responses against HIV infected cells. In a first aspect, a TCR fusion polypeptide comprises a TCR variable alpha (Vα) domain, a TCR variable beta domain (Vβ) and a TCR constant region domain (C), wherein the TCR fusion polypeptide is specific for HIV peptides.
1. A polypeptide comprising a single chain T cell receptor (scTCR) comprising a variable alpha (Vα) domain, a variable beta domain (Vβ) and a constant region domain (C), wherein the Vα and Vβ domains each have at least 85% sequence identity to a scTCR selected from the group consisting of SEQ ID Nos: 2, 4, 6, 8, 10, 12, 14, 16, and 18, and wherein the complementarity determining regions (CDRs) of the Vα domain each have 100% identity to the Vα CDRs of the scTCR, and wherein the CDRs of the VB domain each have 100% identity to the Vβ CDRs of the scTCR.
2. The polypeptide of claim 1 , wherein the polypeptide has at least 90% sequence identity to SEQ ID NO: 2.
3. The polypeptide of claim 2 , wherein the polypeptide has 100% sequence identity to SEQ ID NO: 2.
4. The polypeptide of claim 1 , further comprising a CD3 signaling domain or a CD28 signaling domain.
5. A polynucleotide, wherein the nucleic acid sequence encodes the polypeptide of claim 1 .
6. The polynucleotide of claim 5 , wherein the nucleic acid sequence is selected from the group consisting of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, and 17.
7. The polynucleotide of claim 5 , further comprising a nucleic acid sequence encoding an immune signaling domain, a transmembrane domain, a cytoplasmic domain, a biologically active domain, or a combination thereof.
8. The polynucleotide of claim 7 , wherein the biologically active domain is selected from the group consisting of a cytokine, a checkpoint inhibitor, an antigen specific antibody domain, an enzyme, and a combination thereof.
9. An isolated cell comprising a polynucleotide according to claim 5 .
10. The isolated cell of claim 9 , wherein the isolated cell is an autologous cell.
11. A method of targeting a staining or therapeutic agent to an HIV infected cell in a subject in need thereof, the method comprising administering to the subject an effective amount of a staining or therapeutic agent, wherein the staining or therapeutic agent comprises the scTCR of claim 1 .