ANTIGEN-BINDING PROTEINS TARGETING SHARED ANTIGENS
Provided herein are HLA-PEPTIDE targets and antigen binding proteins that bind HLA-PEPTIDE targets. Also disclosed are methods for identifying the HLA-PEPTIDE targets as well as identifying one or more antigen binding proteins that bind a give n HLA-PEPTIDE target.
1 - 96 . (canceled)
97 . An isolated HLA-PEPTIDE target, wherein the HLA-PEPTIDE target comprises an HLA-restricted peptide complexed with an HLA Class I molecule, wherein the HLA-restricted peptide is located in the peptide binding groove of an α1/α2 heterodimer portion of the HLA Class I molecule, and wherein the HLA-PEPTIDE target is selected from Table A, with the proviso that the isolated HLA-PEPTIDE target is not any one of Target nos. 6364-6369, 6386-6389, 6500, 6521-6524, or 6578 and is not an HLA-PEPTIDE target found in Table B or Table C.
98 . The isolated HLA-PEPTIDE target of claim 97 , wherein
a. the HLA Class I molecule is HLA subtype A*02:01 and the HLA-restricted peptide comprises the sequence LLASSILCA,
b. the HLA Class I molecule is HLA subtype A*01:01 and the HLA-restricted peptide comprises the sequence EVDPIGHLY,
c. the HLA Class I molecule is HLA subtype B*44:02 and the HLA-restricted peptide comprises the sequence GEMSSNSTAL,
d. the HLA Class I molecule is HLA subtype A*02:01 and the HLA-restricted peptide comprises the sequence GVYDGEEHSV,
e. the HLA Class I molecule is HLA subtype *01:01 and the HLA-restricted peptide comprises the sequence EVDPIGHVY, or
f. the HLA Class I molecule is HLA subtype HLA-A*01:01 and the HLA-restricted peptide comprises the sequence NTDNNLAVY.
99 . The isolated HLA-PEPTIDE target of claim 98 , comprising HLA subtype A*02:01 complexed with a restricted peptide consisting of or consisting essentially of the sequence LLASSILCA.
100 . The isolated HLA-PEPTIDE target of claim 97 , wherein the HLA-restricted peptide is between about 5-15 amino acids in length or between about 8-12 amino acids in length.
101 . (canceled)
102 . (canceled)
103 . The isolated HLA-PEPTIDE target of claim 97 , wherein the association of the HLA subtype with the restricted peptide stabilizes non-covalent association of the β2-microglobin subunit of the HLA subtype with the α-subunit of the HLA subtype.
104 . The isolated HLA-PEPTIDE target of claim 103 , wherein the stabilized association of the β2-microglobin subunit of the HLA subtype with the α-subunit of the HLA subtype is demonstrated by conditional peptide exchange.
105 . The isolated HLA-PEPTIDE target of claim 97 , further comprising an affinity tag.
106 - 110 . (canceled)
111 . A composition comprising the HLA-PEPTIDE target of claim 97 attached to a solid support.
112 . The composition of claim 111 , wherein the solid support comprises a bead, well, membrane, tube, column, plate, sepharose, magnetic bead, or chip.
113 . The composition of claim 111 , wherein the HLA-PEPTIDE target comprises a first member of an affinity binding pair and the solid support comprises a second member of the affinity binding pair.
114 . (canceled)
115 . (canceled)
116 . A reaction mixture comprising
a. the isolated HLA-PEPTIDE target of claim 97 ; and
b. a plurality of T-cells isolated from a human subject.
117 . (canceled)
118 . (canceled)
119 . A kit for expressing a stable HLA-PEPTIDE target, comprising a first construct comprising a first nucleic acid sequence encoding an HLA-restricted peptide as defined in claim 97 operably linked to a promoter; and instructions for use in expressing the stable HLA-PEPTIDE complex.
120 - 150 . (canceled)
151 . A composition comprising (i) at least one HLA-PEPTIDE target of claim 97 and (ii) an adjuvant or a pharmaceutically acceptable excipient.
152 - 162 . (canceled)
163 . A method of identifying an antigen binding protein, comprising obtaining at least one HLA-PEPTIDE target listed in Table A; administering the HLA-PEPTIDE target to a subject, optionally in combination with an adjuvant; and isolating the antigen binding protein from the subject.
164 . The method of claim 163 , wherein isolating the antigen binding protein comprises screening the serum of the subject to identify the antigen binding protein.
165 . The method of claim 163 , further comprising contacting the antigen binding protein with one or more peptide-HLA complexes that are distinct from the HLA-PEPTIDE target to determine if the antigen binding protein selectively binds to the HLA-PEPTIDE target, optionally wherein selectivity is determined by measuring binding affinity of the antigen binding protein to soluble target HLA-PEPTIDE complexes versus soluble HLA-PEPTIDE complexes that are distinct from target complexes, optionally wherein selectivity is determined by measuring binding affinity of the antigen binding protein to target HLA-PEPTIDE complexes expressed on the surface of one or more cells versus HLA-PEPTIDE complexes that are distinct from target complexes expressed on the surface of one or more cells.
166 . (canceled)
167 . The method of claim 163 , wherein isolating the antigen binding protein comprises isolating a B cell from the subject that expresses the antigen binding protein and optionally directly cloning sequences encoding the antigen binding protein from the isolated B cell.
168 . The method of claim 167 , further comprising (i) creating a hybridoma using the B cell, (ii) cloning CDRs from the B cell, (iii) immortalizing the B cell, or (iv) creating a library that comprises the antigen binding protein of the B cell.
169 - 172 . (canceled)
173 . A method of identifying an antigen binding protein, comprising contacting a cell with an HLA-multimer comprising at least one HLA-PEPTIDE target listed in Table A; and identifying the antigen binding protein via binding between the HLA-multimer and the antigen binding protein.
174 . (canceled)
175 . The method of claim 173 , wherein the cell is a T cell.
176 - 178 . (canceled)
179 . A method of identifying an antigen binding protein, comprising obtaining the HLA-PEPTIDE target of claim 97 ; administering the HLA-PEPTIDE target to a subject, optionally in combination with an adjuvant; and isolating the antigen binding protein from the subject.
180 . A method of identifying an antigen binding protein, comprising contacting a cell with an HLA-multimer comprising the HLA-PEPTIDE target of claim 97 ; and identifying the antigen binding protein via binding between the HLA-multimer and the antigen binding protein.